Podcasts about osteocalcin

In this episode, I discuss how different forms of exercise impact brain health and performance in both the short and long term. I explain how many of the positive effects of exercise on brain function occur through the action of specific neurochemicals that increase alertness. I also cover how to best time exercise and which specific types of exercise to include in your weekly routine to maximize benefits for your brain. Additionally, I explain how certain types of exercise trigger the release of a hormone from your bones called osteocalcin, as well as brain-derived neurotrophic factor. Together, these substances increase neuroplasticity and enhance learning. The positive effects of exercise on brain oxygenation, blood supply, and fuel utilization are also discussed. Listeners will learn how to design a weekly exercise program that optimizes physical fitness, brain health, longevity, and performance, along with the mechanistic logic behind those recommendations. Find show notes with articles, resources and more at hubermanlab.com. Pre-order Andrew's upcoming book, Protocols: https://go.hubermanlab.com/protocols Thank you to our sponsors AG1: https://drinkag1.com/huberman BetterHelp: https://betterhelp.com/huberman Helix Sleep: https://helixsleep.com/huberman David: https://davidprotein.com/huberman Function: https://functionhealth.com/huberman Maui Nui: https://mauinui.com/huberman Timestamps 00:00:00 Exercise, Brain Health & Performance; Protocols Book 00:04:03 Sponsors: BetterHelp & Helix Sleep 00:06:55 Brain Health, Cardiovascular & Resistance Training 00:11:51 Exercise & Positive Impact on Brain Performance; Arousal 00:18:20 Learning & Arousal 00:23:18 Sponsors: AG1 & David 00:26:01 Exercise & Acute Learning 00:29:16 Tool: High-Intensity Training & Cognitive Flexibility; Over-Training 00:33:32 Long-Term Brain Health; Tool: Exercise “Snacks”, Cognitive Performance 00:36:57 Exercise, Brain & Body Energy, Adrenaline, Norepinephrine 00:44:08 Adrenal “Burnout”?; Exercise to Increase Energy, Adrenaline 00:48:20 Tool: Core, Compound Movements; Mind-Body Connection 00:53:58 Sponsor: Function 00:55:45 Bones, Osteocalcin, BDNF & Hippocampus; Tool: Jump Training 01:01:30 Exercise, Fuel, Multifactorial Pathways; BDNF & Activity 01:05:06 Lactate, Astrocytes & Brain Function; VEGF & Brain Health 01:11:17 Tools: Zone 2, High-Intensity Training, Time Under Tension Training 01:19:54 Sponsor: Maui Nui 01:21:37 Tools: Time Under Tension; Explosive Jumping, Eccentric Control Training 01:25:30 Injury & Exercise, Illness 01:28:09 Sleep; Injury, Sleep-Deprivation & Exercise 01:33:51 SuperAgers, Anterior Mid-Cingulate Cortex, Grit & Persistence 01:42:04 Tool: Embrace Challenges; Deliberate Cold Exposure, Rope Flow 01:47:39 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures

In this insightful interview, PhD researcher Isabella Cooper dives deep into the science of ketosis and its impact on health. She discusses how it's not just about maintaining high levels of ketones but also about the quality and source of those ketones. Isabella highlights the importance of avoiding unhealthy fats and proteins like soybean oil, canola oil, and pea protein isolate while following a ketogenic diet. Discover the latest research findings on cycling in and out of ketosis and how it can influence your overall health. Learn about the molecular components that truly matter when optimizing your metabolic state and achieving sustainable health outcomes. Tune in to explore the fascinating world of metabolic health with Dr. Isabella Cooper and uncover practical tips for enhancing your ketogenic journey! *Experts Featured* Isabella Cooper, PhD University of Westminster https://www.foreveryounggroup.com/ https://www.facebook.com/bellamitochondria X: @I_mitochondria *Related Papers* _Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females_ https://www.mdpi.com/1422-0067/24/21/15621 _Ketosis Suppression and Ageing (KetoSAge) Part 2: The Effect of Suppressing Ketosis on Biomarkers Associated with Ageing, HOMA-IR, Leptin, Osteocalcin, and GLP-1, in Healthy Females_ https://www.mdpi.com/2227-9059/12/7/1553 *Resources* Metabolic Mind's Families & Peers page: https://www.metabolicmind.org/families-and-peers Clinician Directory: https://www.diagnosisdiet.com/directory Follow our channel for more information and education from Bret Scher, MD, FACC, including interviews with leading experts in Metabolic Psychiatry. Learn more about metabolic psychiatry and find helpful resources at https://metabolicmind.org/ About us: Metabolic Mind is a non-profit initiative of Baszucki Group working to transform the study and treatment of mental disorders by exploring the connection between metabolism and brain health. We leverage the science of metabolic psychiatry and personal stories to offer education, community, and hope to people struggling with mental health challenges and those who care for them. Our channel is for informational purposes only. We are not providing individual or group medical or healthcare advice nor establishing a provider-patient relationship. Many of the interventions we discuss can have dramatic or potentially dangerous effects if done without proper supervision. Consult your healthcare provider before changing your lifestyle or medications. #MetabolicMind #MetabolicNeuroscience #KetogenicMetabolicTherapy #NutritionalKetosis#AlternativeTreatment#MedicalKeto#KetogenicTherapy #MetabolicHealth#Keto#Longevity

Sarah Ann is joined by practitioner and co-founder of Sensate, Stefan Chmelik, to explore how the mind-blowing Vagus Nerve could hold the answer to improving your mental and physical health.Discover what methods you can use to lower your stress, anxiety and reduce your chances of developing chronic disease.Listen to the full episode hereWatch the full episode Youtube here Follow me, Sarah Ann Macklin on Instagram

Vitamin K ist sprichwörtlich in aller Munde. Meistens über die normale Ernährung oder als Nahrungsergänzungsmittel, auf jeden FAll aber als Frage von Patientinnen und Patienten in der täglichen Sprechstunde. Daher wollen wir uns in dieser Folge intensiver mit dem Thema Vitamin K, K1 und K2 und Knochenstoffwechsel beschäftigen.

Bone is not just a passive scaffold that supports our body. It is also an active endocrine organ that secretes hormones that regulate various aspects of our physiology, from energy metabolism to brain function. One of these hormones is osteocalcin, which has been extensively studied by Gerard Karsently and his team at Columbia University. In this podcast, we will explore the fascinating discoveries that Karsently and his colleagues have made about osteocalcin and its role in health and disease. Osteocalcin is a protein that is produced by bone cells called osteoblasts. It is then released into the bloodstream, where it can reach different organs and tissues and exert its effects. Osteocalcin has been shown to enhance insulin secretion by the pancreas, testosterone production by the testes, muscle function during exercise, memory formation and mood regulation by the brain, and even the ability to cope with stress. Osteocalcin also has anti-aging properties, as it can prevent or reverse some of the decline in physiological functions that occurs with age. The levels of osteocalcin in the blood are not constant. They vary depending on several factors, such as diet, exercise, stress and age. These interactions create a complex network of communication between bone and other organs that helps to maintain homeostasis and adapt to changing conditions. Karsently's research has opened new avenues for understanding the biology of bone and its impact on whole-body physiology. It has also revealed new potential therapeutic targets or strategies for treating or preventing various metabolic, reproductive, cognitive and emotional disorders. In this podcast, we will dive deeper into the fascinating world of osteocalcin and bone endocrinology with Gerard Karsently himself. Useful Links: Berger JM, Karsenty G. Osteocalcin and the physiology of danger. FEBS Lett. 2022;596(5):665-680. doi:10.1002/1873-3468.1425

Question: If undercarboxylated osteocalcin has health benefits, and vitamin K2 decreases it, what does that mean for K2 supplementation? Short Answer: Vitamin K2 helps secure osteocalcin in bone matrix, where it is decarboxylated and released as an endocrine hormone in response to certain stimuli. When released, it acts to optimize insulin secretion, insulin sensitivity, fuel use during exercise, and male testosterone. This is a clip from a live Q&A session open to CMJ Masterpass members. In addition to this episode, you can access two other free samples using this link: https://chrismasterjohnphd.substack.com/p/questions-on-phosphatidylcholine In that batch of free episodes you will also find the answers to these questions: Phosphatidylcholine and TMAO What to Do About Twitching If you want to become a Masterpass member so you can participate in the next live Q&A, or so you can have access to the complete recording and transcript of each Q&A session, you can save 10% off the subscription price for as long as you remain a member by using this link to sign up: https://chrismasterjohnphd.substack.com/qanda Learn more about the Masterpass here: https://chrismasterjohnphd.substack.com/about This snippet is from the December 14, 2022 AMA. The full recording and transcript is reserved for Masterpass members. Here is a preview of what's included: Inositol, What Is It Good For? If I am at risk of heart disease, and phosphatidylcholine raises my TMAO, should I stop the supplement? Maragen Calcium Could slow methylation cause high selenium levels? My current thoughts on cholesterol and heart disease If I already have oxidative stress, what ducks should I have in a row before supplementing with iron? Is it safe to take eight milligrams of zinc daily without copper? What to do about developing sensitivities to an increasingly broad range of foods? What else to do about hemochromatosis besides phlebotomy? If gestational diabetes is just a biotin deficiency, why are women who are insulin resistant prior to pregnancy at higher risk for it, including women with PCOS? What to do about chronically elevated amylase and lipase? What to do about a non-drinker having very high GGT and occasionally high ALT? What are the most common vitamin and mineral deficiencies? What are the best supplements, vitamins, and minerals for OCD and depression? What is the connection between low pyruvate and high ketones? Is high LDL a concern if the carotid IMT and coronary calcium scan are clear?  An algorithm to fix twitching Do I trust food allergy tests? Here's a link to the full AMA: https://chrismasterjohnphd.substack.com/p/recording-and-transcript-of-the-december Access the show notes, transcript, and comments here.

In this episode, Tim will be interviewing our Chief Psychology Officer - Dr Amanda Potter and Claire Dale, the author of Physical Intelligence, to understand the importance of Physical Intelligence in creating physical, emotional and mental stamina and staying power. The interview will look at tips for energy maintenance and for endurance. Amanda will also touch on the role of each of the hormones and neurotransmitters in happiness, success and well being.In this episode, Claire and Amanda are being interviewed by Tim Hepworth. The Chief Psychology Officer website is now available https://www.thecpo.co.uk/To contact Amanda and Claire via LinkedIn: linkedin.com/in/amandapotterzirconlinkedin.com/in/claire-daleTo order a copy of 'Physical Intelligence', go to:https://www.amazon.co.uk/Claire-Dale/e/B07P9NWZGJ/ref=dp_byline_cont_pop_book_1If you are interested in Claire's Physical Intelligence Coaching Course please go to: www.coachwithpi.com, or for more information about Claire and her corporate work please go to www.companiesinmotion.com.TimestampsBuilding Endurance & Stamina·       00:00 – Introduction to Building Endurance·       00:30 – Claire Dale: Career History·       03:30 – Why Physical Intelligence?·       04:23 – Things to learn from this·       04:52 – What is Physical Intelligence?·       05:19 – Things are happening to your body…Chemistry is the study of change…·       06:03 – Neuroscience & Interpretation·       06:48 – Balancing act of chemistry·       08:08 – Visualization revisited·       09:00 – Personal Interaction·       09:25 – Oxytocin·       10:18 – We all love Neuroscience·       11:02 – Breathing seems pretty important…·       13:18 – The Importance of regulating breathingFruit for the mind·       14:07 – Nature vs. Nurture·       15:00 – Personal Perspective·       16:02 – Out of balance·       16:26 – In control… In control…·       17:16 – Neuroplasticity·       18:02 – Hands in the air like you care·       18:48 – Dopamine·       19:38 – Doing this Podcast helps keeps us youngKeep on movin'·       20:00 – What is beneficial to our lives·       20:42 – It's not figurative; its literal·       21:15 – Dopamine is motivation, not reward·       22:26 – Exercise is good for you·       23:33 – Aerobics·       24:04 – Our approach to Exercise·       24:51 – BDNF·       26:29 – Stamina & Staying Power·       27:07 – RESISTANCE (training) IS USEFUL!·       28:32 – Cortisol & Testosterone·       29:35 – Myokines & Osteocalcin·       30:26 – Summary of the links·       31:15 – DHEAWays of Improving Physical Intelligence·       32:13 – Remote working·       32:45 – The right choices·       35:26 – Tips for Physical Intelligence·       37:02 – The end.

Huberman Lab Podcast Notes Key Takeaways New memories are formed through repetition or immensely positive/negative eventsEmotionality and emotion experienced after an event dictates whether you will learn it quicklyMemories are formed because of a neurochemical state (release of adrenaline, cortisol, epinephrine, norepinephrine) that takes place following an emotion – not because something evokes emotion itselfTiming of caffeine for memory and learning enhancement matters: consume caffeine immediately after or 5-15 minutes after repetitionTo optimize learning: immediately after learning, put the body into a heightened state of emotionality and alertness (e.g., caffeine, cold exposure); hours later, a nap (28-90 minutes) or non-sleep deep rest is critical for learning and memoryAnything that increases adrenaline will increase learning and memory and reduce the number of repetitions required to learn something (regardless of whether there's emotion attached)Anything that reduces epinephrine and adrenaline will impair learningChronic stress and elevation of epinephrine are detrimental to memory and learning (among many other things)Physical movement can enhance cognitive ability and ability to learn new skills – shoot for 180-200 minutes of zone 2 cardio per week and a few sessions of load-bearing exercise per weekTaking a mental snapshot (blinking and imagining you are taking a photo of something) actually stamps down visual memory almost as much as taking an actual photoMeditation can improve attention, memory, mood, and emotion regulation but timing matters! If you meditate too late, it may actually hinder sleep because you are in a calm but highly attentional stateAs always, start with behavioral tools before exploring pharmacologyRead the full notes @ podcastnotes.orgThis episode I explain the mechanisms by which different types of memories are established in our brain and how to leverage the amount and timing of key neurochemicals and hormones, such as adrenaline (aka epinephrine) and cortisol, to improve your learning and memory abilities. I describe multiple science-based protocols to do this, including repetition, caffeine, emotional states, deliberate cold exposure, sleep, meditation, and the role of vision, including taking “mental snapshots.” I also describe how exercise and an associated hormone, osteocalcin, can improve cognitive ability and memory formation. I also describe unique aspects and forms of memory such as photographic memory, extreme facial recognition (aka super recognition), and the phenomenon known as déjà vu. Thank you to our sponsors Eight Sleep: https://www.eightsleep.com/huberman Thesis: https://takethesis.com/huberman InsideTracker: https://insidetracker.com/huberman Our Patreon page https://www.patreon.com/andrewhuberman Supplements from Momentous https://www.livemomentous.com/huberman. For the full show notes, visit hubermanlab.com. Timestamps (00:00:00) Memory, Improving Memory   (00:02:45) Eight Sleep, Thesis, InsideTracker  (00:07:54) Sensory Stimuli, Nervous System & Encoding Memory  (00:11:12) Context & Memory Formation  (00:13:46) Tool: Repetition, Improving Learning & Memory  (00:17:11) Co-Activation and intensity Neuron Activation   (00:20:50) Different Types of Memory (00:25:40) Memory Formation in the Brain, Hippocampus  (00:28:00) Hippocampus, Role in Memory & Learning, Explicit vs. Implicit Memory (00:31:49) Emotion & Memory Enhancement  (00:36:44) Tool: Emotion Saliency & Improved Memory (00:41:42) Conditioned-Placed Avoidance/Preference, Adrenaline  (00:47:14) Adrenaline & Cortisol   (00:49:35) Accelerating the Repetition Curve & Adrenaline  (00:53:03) Tool: Enhancing Learning & Memory - Caffeine, Alpha-GPC & Stimulant Timing (01:00:50) Tool: Enhancing Learning & Memory - Sleep, Non-Sleep Deep Rest (NSDR) (01:04:48) Tool: Enhancing Learning & Memory - Deliberate Cold Exposure, Adrenaline (01:08:42) Timing of Adrenaline Release & Memory Formation  (01:12:36) Chronically High Adrenaline & Cortisol, Impact on Learning & Memory  (01:15:12) Adrenaline Linked with Learning: Not a New Principle  (01:17:25) Amygdala, Adrenaline & Memory Formation, Generalization of Memories (01:22:20) Tool: Cardiovascular Exercise & Neurogenesis  (01:27:00) Cardiovascular Exercise, Osteocalcin & Improved Hippocampal Function (01:29:59) Load-Bearing Exercise, Osteocalcin & Cognitive Ability  (01:34:41) Tool: Timing of Exercise, Learning & Memory Enhancement (01:37:29) Photographic Memory (01:38:49) “Super Recognizers,” Facial Recognition    (01:41:46) Tool: Mental Snapshots, Photographs & Memory Enhancement (01:49:12) Déjà Vu (01:53:24) Tool: Meditation, Daily Timing of Meditation (02:02:21) How to Enhance Memory  (02:05:51) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Patreon, Momentous Supplements, Instagram, Twitter, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·Jubilee website·PrevMed's website·PrevMed's YouTube channel·PrevMed's Facebook page·PrevMed's Instagram·PrevMed's LinkedIn·PrevMed's Twitter ·PrevMed's Pinterest

This episode I explain the mechanisms by which different types of memories are established in our brain and how to leverage the amount and timing of key neurochemicals and hormones, such as adrenaline (aka epinephrine) and cortisol, to improve your learning and memory abilities. I describe multiple science-based protocols to do this, including repetition, caffeine, emotional states, deliberate cold exposure, sleep, meditation, and the role of vision, including taking “mental snapshots.” I also describe how exercise and an associated hormone, osteocalcin, can improve cognitive ability and memory formation. I also describe unique aspects and forms of memory such as photographic memory, extreme facial recognition (aka super recognition), and the phenomenon known as déjà vu. Thank you to our sponsors Eight Sleep: https://www.eightsleep.com/huberman Thesis: https://takethesis.com/huberman InsideTracker: https://insidetracker.com/huberman Our Patreon page https://www.patreon.com/andrewhuberman Supplements from Momentous https://www.livemomentous.com/huberman. For the full show notes, visit hubermanlab.com. Timestamps (00:00:00) Memory, Improving Memory   (00:02:45) Eight Sleep, Thesis, InsideTracker  (00:07:54) Sensory Stimuli, Nervous System & Encoding Memory  (00:11:12) Context & Memory Formation  (00:13:46) Tool: Repetition, Improving Learning & Memory  (00:17:11) Co-Activation and intensity Neuron Activation   (00:20:50) Different Types of Memory (00:25:40) Memory Formation in the Brain, Hippocampus  (00:28:00) Hippocampus, Role in Memory & Learning, Explicit vs. Implicit Memory (00:31:49) Emotion & Memory Enhancement  (00:36:44) Tool: Emotion Saliency & Improved Memory (00:41:42) Conditioned-Placed Avoidance/Preference, Adrenaline  (00:47:14) Adrenaline & Cortisol   (00:49:35) Accelerating the Repetition Curve & Adrenaline  (00:53:03) Tool: Enhancing Learning & Memory - Caffeine, Alpha-GPC & Stimulant Timing (01:00:50) Tool: Enhancing Learning & Memory - Sleep, Non-Sleep Deep Rest (NSDR) (01:04:48) Tool: Enhancing Learning & Memory - Deliberate Cold Exposure, Adrenaline (01:08:42) Timing of Adrenaline Release & Memory Formation  (01:12:36) Chronically High Adrenaline & Cortisol, Impact on Learning & Memory  (01:15:12) Adrenaline Linked with Learning: Not a New Principle  (01:17:25) Amygdala, Adrenaline & Memory Formation, Generalization of Memories (01:22:20) Tool: Cardiovascular Exercise & Neurogenesis  (01:27:00) Cardiovascular Exercise, Osteocalcin & Improved Hippocampal Function (01:29:59) Load-Bearing Exercise, Osteocalcin & Cognitive Ability  (01:34:41) Tool: Timing of Exercise, Learning & Memory Enhancement (01:37:29) Photographic Memory (01:38:49) “Super Recognizers,” Facial Recognition    (01:41:46) Tool: Mental Snapshots, Photographs & Memory Enhancement (01:49:12) Déjà Vu (01:53:24) Tool: Meditation, Daily Timing of Meditation (02:02:21) How to Enhance Memory  (02:05:51) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Patreon, Momentous Supplements, Instagram, Twitter, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

Huberman Lab Podcast Notes Key Takeaways Intermittent challenges or stressors to your system are good – humans are evolved for challenges, but today's lifestyle has taken away most of the common struggles we experienced beforeThree key nutrients for the brain and body: (1) sulforaphane; (2) omega-3; (3) vitamin DFood sources of sulforaphane: broccoli (barely cooked), broccoli sprouts, moringa powder“I personally think [omega-3 fish oil] is one of the most powerful anti-inflammatory things, dietary lifestyle things we can get easily that is going to powerfully modulate the way you think, the way you feel, and the way you age.” – Dr. Rhonda PatrickVitamin D is not just a vitamin! 70% of the US population is deficient – it's worth measuring & supplementing to optimal bone health, immunity, hormone conversion, and moreThere's a strong dose-dependent nature of sauna use: people who use sauna 4-7x/week have a lower risk (60% reduction) of dementia and Alzheimer's; people who use sauna 2-3x/week have a 20% reduction in riskHeat stress mimics moderate cardiovascular exercise effect – this could be a great onramp for people who are otherwise unable to exercise due to disability or whatever reasonThe cardiorespiratory system is improved in people who do both sauna and exercise compared to doing either aloneStress & memory: if you're too relaxed you won't remember things as well; at peak levels of stress, you remember things better until you reach too high a level of panic               Read the full notes @ podcastnotes.orgMy guest is Rhonda Patrick, Ph.D. She earned her doctoral degree in biomedical science from St. Jude Children's Research Hospital at the University of Tennessee Health Science Center and has become one of the leading public health educators on the brain and general health, aging, cancer, and nutrition. We discuss the four major categories of micronutrients that regulate cellular and organ stress and antioxidants, inflammation, hormone regulation, immune system, and longevity. Dr. Patrick provides actionable protocols for obtaining key micronutrients from food and/or supplement-based sources. Additionally, Dr. Patrick outlines protocols for deliberate cold and deliberate heat exposure to benefit metabolism, cardiorespiratory fitness, mental health, and lifespan.  Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Thesis: https://takethesis.com/huberman InsideTracker: https://insidetracker.com/huberman See Andrew Huberman Live: The Brain Body Contract Tuesday, May 17th: Seattle, WA Wednesday, May 18th: Portland, OR https://hubermanlab.com/tour Our Patreon page https://www.patreon.com/andrewhuberman Supplements from Momentous https://www.livemomentous.com/huberman. For the full show notes, visit hubermanlab.com. Timestamps (00:00:00) Dr. Rhonda Patrick – Micronutrients, Cold & Heat Exposure  (00:03:12) Momentous Supplements (00:04:27) The Brain-Body Contract  (00:05:30) AG1 (Athletic Greens), Thesis, InsideTracker (00:09:42) Stress Response Pathways, Hormesis (00:16:38) Plants, Polyphenols, Sulforaphane (00:21:12) Tools 1: Sulforaphane - Broccoli Sprouts, Broccoli, Mustard Seed  (00:23:50) Tool 2: Moringa & Nrf2 Antioxidant Response (00:25:25) Sulforaphane: Antioxidants (Glutathione) & Air Pollution (Benzene Elimination)  (00:27:10) Plants & Stress Response Pathways, Intermittent Challenges  (00:29:35) Traumatic Brain Injury, Sulforaphane, Nrf2  (00:35:08) Tools 3: Omega-3 Fatty Acids (ALA, EPA & DHA), Fish Oil, Oxidation  (00:48:40) EPA Omega-3s & Depression  (00:52:02) Krill Oil vs. Fish Oil Supplements?  (00:54:23) Benefits of Omega-3 Fatty Acids, Omega-3 Index & Life Expectancy  (00:59:24) Tool 4: Food Sources of EPA Omega-3s  (01:06:07) Omega-3 Supplementation, Omega-3 Index Testing (01:10:22) Benefits of Omega-3s  (01:14:40) Tool 5: Food Sources of DHA Omega-3s (01:17:07) Vitamin D & Sun Skin Exposure  (01:22:18) Role of Vitamin D, Gene Regulation  (01:25:30) Tool 6: Vitamin D Testing & Vitamin D3 Supplementation  (01:33:15) Tool 7: Skin Surface Area & Sun Exposure, Vitamin D  (01:34:23) Vitamin D & Longevity (01:36:46) Sun Exposure & Sunscreen (01:40:30) Role of Magnesium, Magnesium Sources, Dark Leafy Green Vegetables (01:44:50) Tool 8: Magnesium Supplements: Citrate, Threonate, Malate, Bisglycinate  (01:50:57) Tool 9: Deliberate Cold Exposure Protocol & Mood/Anxiety (01:59:22) Tool 10: Cold Exposure, Mitochondria UCP1 & Heat Generation (02:02:30) Tool 11: Cold & Fat ‘Browning', PGC-1alpha, Metabolism (02:05:08) Cold Exposure & High-Intensity Interval Training (HIIT), PGC-1alpha, Muscle  (02:08:04) Tools 12: Exercise, HIIT, Tabata & Sauna  (02:13:30) Tool 13: Sauna, Endorphins/Dynorphins, Mood  (02:17:45) Tool 14: Mild Stress, Adrenaline & Memory (02:19:53) Sauna, Vasodilation & Alzheimer's and Dementia Risk  (02:25:30) Sauna Benefits, Cardiorespiratory Fitness, Heat Shock Proteins (HSPs)  (02:31:29) Insulin signaling, FOXO3 & Longevity  (02:33:22) Tools 16: Sauna Protocols, Hot Baths & Fertility  (02:37:41) Tool 17: Exercise & Longevity, Osteocalcin  (02:41:37) Tools 18: Red Light Sauna? Infrared Sauna? Sauna & Sweating of Heavy Metals (02:47:20) FoundMyFitness Podcast, Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Patreon, Momentous Supplements, Huberman Lab on Instagram & Twitter Title Card Photo Credit: Mike Blabac Disclaimer

Huberman Lab Podcast Notes Key Takeaways Intermittent challenges or stressors to your system are good – humans are evolved for challenges, but today's lifestyle has taken away most of the common struggles we experienced beforeThree key nutrients for the brain and body: (1) sulforaphane; (2) omega-3; (3) vitamin DFood sources of sulforaphane: broccoli (barely cooked), broccoli sprouts, moringa powder“I personally think [omega-3 fish oil] is one of the most powerful anti-inflammatory things, dietary lifestyle things we can get easily that is going to powerfully modulate the way you think, the way you feel, and the way you age.” – Dr. Rhonda PatrickVitamin D is not just a vitamin! 70% of the US population is deficient – it's worth measuring & supplementing to optimal bone health, immunity, hormone conversion, and moreThere's a strong dose-dependent nature of sauna use: people who use sauna 4-7x/week have a lower risk (60% reduction) of dementia and Alzheimer's; people who use sauna 2-3x/week have a 20% reduction in riskHeat stress mimics moderate cardiovascular exercise effect – this could be a great onramp for people who are otherwise unable to exercise due to disability or whatever reasonThe cardiorespiratory system is improved in people who do both sauna and exercise compared to doing either aloneStress & memory: if you're too relaxed you won't remember things as well; at peak levels of stress, you remember things better until you reach too high a level of panic               Read the full notes @ podcastnotes.orgMy guest is Rhonda Patrick, Ph.D. She earned her doctoral degree in biomedical science from St. Jude Children's Research Hospital at the University of Tennessee Health Science Center and has become one of the leading public health educators on the brain and general health, aging, cancer, and nutrition. We discuss the four major categories of micronutrients that regulate cellular and organ stress and antioxidants, inflammation, hormone regulation, immune system, and longevity. Dr. Patrick provides actionable protocols for obtaining key micronutrients from food and/or supplement-based sources. Additionally, Dr. Patrick outlines protocols for deliberate cold and deliberate heat exposure to benefit metabolism, cardiorespiratory fitness, mental health, and lifespan.  Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Thesis: https://takethesis.com/huberman InsideTracker: https://insidetracker.com/huberman See Andrew Huberman Live: The Brain Body Contract Tuesday, May 17th: Seattle, WA Wednesday, May 18th: Portland, OR https://hubermanlab.com/tour Our Patreon page https://www.patreon.com/andrewhuberman Supplements from Momentous https://www.livemomentous.com/huberman. For the full show notes, visit hubermanlab.com. Timestamps (00:00:00) Dr. Rhonda Patrick – Micronutrients, Cold & Heat Exposure  (00:03:12) Momentous Supplements (00:04:27) The Brain-Body Contract  (00:05:30) AG1 (Athletic Greens), Thesis, InsideTracker (00:09:42) Stress Response Pathways, Hormesis (00:16:38) Plants, Polyphenols, Sulforaphane (00:21:12) Tools 1: Sulforaphane - Broccoli Sprouts, Broccoli, Mustard Seed  (00:23:50) Tool 2: Moringa & Nrf2 Antioxidant Response (00:25:25) Sulforaphane: Antioxidants (Glutathione) & Air Pollution (Benzene Elimination)  (00:27:10) Plants & Stress Response Pathways, Intermittent Challenges  (00:29:35) Traumatic Brain Injury, Sulforaphane, Nrf2  (00:35:08) Tools 3: Omega-3 Fatty Acids (ALA, EPA & DHA), Fish Oil, Oxidation  (00:48:40) EPA Omega-3s & Depression  (00:52:02) Krill Oil vs. Fish Oil Supplements?  (00:54:23) Benefits of Omega-3 Fatty Acids, Omega-3 Index & Life Expectancy  (00:59:24) Tool 4: Food Sources of EPA Omega-3s  (01:06:07) Omega-3 Supplementation, Omega-3 Index Testing (01:10:22) Benefits of Omega-3s  (01:14:40) Tool 5: Food Sources of DHA Omega-3s (01:17:07) Vitamin D & Sun Skin Exposure  (01:22:18) Role of Vitamin D, Gene Regulation  (01:25:30) Tool 6: Vitamin D Testing & Vitamin D3 Supplementation  (01:33:15) Tool 7: Skin Surface Area & Sun Exposure, Vitamin D  (01:34:23) Vitamin D & Longevity (01:36:46) Sun Exposure & Sunscreen (01:40:30) Role of Magnesium, Magnesium Sources, Dark Leafy Green Vegetables (01:44:50) Tool 8: Magnesium Supplements: Citrate, Threonate, Malate, Bisglycinate  (01:50:57) Tool 9: Deliberate Cold Exposure Protocol & Mood/Anxiety (01:59:22) Tool 10: Cold Exposure, Mitochondria UCP1 & Heat Generation (02:02:30) Tool 11: Cold & Fat ‘Browning', PGC-1alpha, Metabolism (02:05:08) Cold Exposure & High-Intensity Interval Training (HIIT), PGC-1alpha, Muscle  (02:08:04) Tools 12: Exercise, HIIT, Tabata & Sauna  (02:13:30) Tool 13: Sauna, Endorphins/Dynorphins, Mood  (02:17:45) Tool 14: Mild Stress, Adrenaline & Memory (02:19:53) Sauna, Vasodilation & Alzheimer's and Dementia Risk  (02:25:30) Sauna Benefits, Cardiorespiratory Fitness, Heat Shock Proteins (HSPs)  (02:31:29) Insulin signaling, FOXO3 & Longevity  (02:33:22) Tools 16: Sauna Protocols, Hot Baths & Fertility  (02:37:41) Tool 17: Exercise & Longevity, Osteocalcin  (02:41:37) Tools 18: Red Light Sauna? Infrared Sauna? Sauna & Sweating of Heavy Metals (02:47:20) FoundMyFitness Podcast, Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Patreon, Momentous Supplements, Huberman Lab on Instagram & Twitter Title Card Photo Credit: Mike Blabac Disclaimer

My guest is Rhonda Patrick, Ph.D. She earned her doctoral degree in biomedical science from St. Jude Children's Research Hospital at the University of Tennessee Health Science Center and has become one of the leading public health educators on the brain and general health, aging, cancer, and nutrition. We discuss the four major categories of micronutrients that regulate cellular and organ stress and antioxidants, inflammation, hormone regulation, immune system, and longevity. Dr. Patrick provides actionable protocols for obtaining key micronutrients from food and/or supplement-based sources. Additionally, Dr. Patrick outlines protocols for deliberate cold and deliberate heat exposure to benefit metabolism, cardiorespiratory fitness, mental health, and lifespan.  Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman Thesis: https://takethesis.com/huberman InsideTracker: https://insidetracker.com/huberman See Andrew Huberman Live: The Brain Body Contract Tuesday, May 17th: Seattle, WA Wednesday, May 18th: Portland, OR https://hubermanlab.com/tour Our Patreon page https://www.patreon.com/andrewhuberman Supplements from Momentous https://www.livemomentous.com/huberman. For the full show notes, visit hubermanlab.com. Timestamps (00:00:00) Dr. Rhonda Patrick – Micronutrients, Cold & Heat Exposure  (00:03:12) Momentous Supplements (00:04:27) The Brain-Body Contract  (00:05:30) AG1 (Athletic Greens), Thesis, InsideTracker (00:09:42) Stress Response Pathways, Hormesis (00:16:38) Plants, Polyphenols, Sulforaphane (00:21:12) Tools 1: Sulforaphane - Broccoli Sprouts, Broccoli, Mustard Seed  (00:23:50) Tool 2: Moringa & Nrf2 Antioxidant Response (00:25:25) Sulforaphane: Antioxidants (Glutathione) & Air Pollution (Benzene Elimination)  (00:27:10) Plants & Stress Response Pathways, Intermittent Challenges  (00:29:35) Traumatic Brain Injury, Sulforaphane, Nrf2  (00:35:08) Tools 3: Omega-3 Fatty Acids (ALA, EPA & DHA), Fish Oil, Oxidation  (00:48:40) EPA Omega-3s & Depression  (00:52:02) Krill Oil vs. Fish Oil Supplements?  (00:54:23) Benefits of Omega-3 Fatty Acids, Omega-3 Index & Life Expectancy  (00:59:24) Tool 4: Food Sources of EPA Omega-3s  (01:06:07) Omega-3 Supplementation, Omega-3 Index Testing (01:10:22) Benefits of Omega-3s  (01:14:40) Tool 5: Food Sources of DHA Omega-3s (01:17:07) Vitamin D & Sun Skin Exposure  (01:22:18) Role of Vitamin D, Gene Regulation  (01:25:30) Tool 6: Vitamin D Testing & Vitamin D3 Supplementation  (01:33:15) Tool 7: Skin Surface Area & Sun Exposure, Vitamin D  (01:34:23) Vitamin D & Longevity (01:36:46) Sun Exposure & Sunscreen (01:40:30) Role of Magnesium, Magnesium Sources, Dark Leafy Green Vegetables (01:44:50) Tool 8: Magnesium Supplements: Citrate, Threonate, Malate, Bisglycinate  (01:50:57) Tool 9: Deliberate Cold Exposure Protocol & Mood/Anxiety (01:59:22) Tool 10: Cold Exposure, Mitochondria UCP1 & Heat Generation (02:02:30) Tool 11: Cold & Fat ‘Browning', PGC-1alpha, Metabolism (02:05:08) Cold Exposure & High-Intensity Interval Training (HIIT), PGC-1alpha, Muscle  (02:08:04) Tools 12: Exercise, HIIT, Tabata & Sauna  (02:13:30) Tool 13: Sauna, Endorphins/Dynorphins, Mood  (02:17:45) Tool 14: Mild Stress, Adrenaline & Memory (02:19:53) Sauna, Vasodilation & Alzheimer's and Dementia Risk  (02:25:30) Sauna Benefits, Cardiorespiratory Fitness, Heat Shock Proteins (HSPs)  (02:31:29) Insulin signaling, FOXO3 & Longevity  (02:33:22) Tools 16: Sauna Protocols, Hot Baths & Fertility  (02:37:41) Tool 17: Exercise & Longevity, Osteocalcin  (02:41:37) Tools 18: Red Light Sauna? Infrared Sauna? Sauna & Sweating of Heavy Metals (02:47:20) FoundMyFitness Podcast, Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Patreon, Momentous Supplements, Huberman Lab on Instagram & Twitter Title Card Photo Credit: Mike Blabac Disclaimer

"how does Neoprene training and Osteocalcin fit into the Q-training"  good question btw "what is emotional mapping"

The science is full of relationships between osteocalcin and diabetes. Osteocalcin is critical to bone growth and autophagy. It also appears to increase insulin sensitivity. And remember that vitamin K2 is required to activate osteocalcin through the process of carboxylation. Does this mean vitamin K2 deficiency can create insulin resistance? I don't know, but it's an interesting thought.For more information, contact us at 859-721-1414 or myhealth@prevmedheartrisk.com. Also, check out the following resources:  ·PrevMed's website·PrevMed's YouTube channel·PrevMed's Facebook page

Welcome back to the Whole View, episode 417, whereby Stacy and you get to be educated on K2. (0:27) This is one of those, "I can't say that I'm disappointed that we are talking about this" shows for Stacy. Although she didn't specifically ask the question, Stacy learned about K2 way back in the day and hasn't learned much since. Sarah is going to fix that today. Before we jump in, we want to thank our returning sponsor Just Thrive. Both Stacy and Sarah have used Just Thrive for years as their probiotic supplement, and swear by their product. Stacy can't encourage everyone to give it a try enough. It is the only one that makes a difference that Stacy can actually feel. Today Just Thrive is actually sponsoring with their K2-7 supplement. If this is something you would like to try, you can get 15% off your order by entering in the code THEWHOLEVIEW when placing your order. This code applies to anything on Just Thrive's site.   Patreon Listener Comments Before we dive into this week's listener questions, we do have some fun comments to read in response to the first bonus audio content posted onto Patreon. (4:49) For those who don't know, this is a newly launched way that you can support us. What we are doing to thank our Patreon family is posting bonus audio once a month, that is our behind the scene thoughts on each episode. This audio is posted for our Patreon family only and is very uncensored. It is uncensored from both the G-rated perspective, but also the level of unfiltered thoughts and viewpoints that Stacy and Sarah are sharing. Kelby wrote, "First episode is

This is a podcast which picks up a few interesting things that have appeared in the news in recent weeks. In this episode we have two stories from science and one on sport. In our first story, we learn that our bones are much more important to our health than just holding our bodies together. You read more about it here: https://www.theguardian.com/science/2020/jul/04/does-the-key-to-anti-ageing-lie-in-our-bones In our second scientific story, we discover that one human year is NOT seven dog years, like we always though. To work out how old a dog is in human years, you need to do this calculation: human age = 16 ln(dog_age) + 31. And you can read more by following this link: https://www.theguardian.com/lifeandstyle/2020/jul/02/every-human-year-not-equivalent-to-seven-dog-years-scientists-find In our story on sport, we hear that the football has started again in Australia. Find out how Essendon are going and learn more by following these links: https://www.essendonfc.com.au/ https://www.afl.com.au/   Worksheet Answers: B 2. D 3. C

In der vorliegenden Arbeit wurde geprüft, wie sich der Anteil an Ω-3-Fettsäuren im Gesamtfettsäuremuster von Pferden nach Fütterung von Algen, die reich an Ω-3-Fettsäuren sind, verändert. Neben Fischöl gelten Mikroalgen als Quelle für die beiden Ω-3-Fettsäuren Eicosapentaensäure (EPA) und Docosahexaensäure (DHA). Positive Effekte von Ω-3-Fettsäuren auf den Knochen werden diskutiert. Aufgrund dessen wurde in der hier durchgeführten Studie erstmals die Wirkung von Ω-3-Fettsäuren auf den Knochenstoffwechsel des Pferdes untersucht. Während des insgesamt 24-wöchigen Versuchs wurden dem Futter von 4 Ponies über einen Zeitraum von 12 Wochen DHA-reiche Mikroalgen (0.32g/kg KM) zugesetzt. Im Serum wurden das Gesamtfettsäuremuster und die Knochenformationsmarker, gesamtalkalische Phosphatase und Osteocalcin bestimmt. Im Urin wurden die Knochenresorptionsmarker Collagen-Crosslinks (Pyridinolin und Desoxypyridinolin) und der Calciumgehalt untersucht. Im Serum der Tiere konnte nach Zusatz der Algen zum Futter ein deutlicher Anstieg der beiden Ω-3-Fettsäuren EPA und DHA auf das 13-fache bzw. das 23-fache nachgewiesen werden. 6 Wochen nach Absetzen der Algensupplementierung wurde die DHA-Konzentration des Ausgangswertes fast wieder erreicht. Die Verabreichung der Omega-Algen führte weder bei den Markern der Knochenformation noch bei den Markern der Knochenresorption zu signifikanten Veränderungen. Es lassen sich lediglich Tendenzen feststellen. Eventuell ist eine längere Verabreichung oder eine höhere Dosierung nötig, um eine Veränderung des Knochenstoffwechsels zu erzielen.

Leptin secreted by adipose tissue decreases insulin production through both direct and indirect mechanisms.

Biochemical markers of bone metabolism have become a common form of analysis for bone metabolism. A number of factors, however, cause fluctuations in these parameters such as day-to-day changes, seasonal changes and age. In women, studies have confirmed parameter fluctuations during the menstrual cycle (Zittermann et al., 2000). Up until now, the coherence hormone status and bone marker activity have been scanty in animal models. The objective of this study was to examine the dependence of bone marker activity on the estrous cycle in the Dresdner miniature pig. The present study included the bone formation marker osteocalcin, and bone resorption marker serum crosslaps. The estrous cycle dependency was determined by comparing the development of marker concentrations with progesterone and estradiol in the respective cycle stages of each pig after synchronisation and at particular sampling points of time. Furthermore the behaviour of biochemical markers, osteocalcin and crosslaps were examined at and after ovariohysterectomy (OVX) to determine the effect of OVX on these specific bone markers. Another aspect of this study was to determine the influence of calcium content in the diet on bone metabolism before and after castration. Sixteen animals were divided into three groups, two control groups and a OVX group. One control group received a 0.99% calcium diet, while the OVX and the second control group received a 0.7% calcium diet. The animals in the OVX group were ovariohysterectomised, while the pigs in the control and the second control groups were not manipulated. The trial consisted of two periods; the pre-castration period, lasting 65 weeks and a post-castration period lasting 8 weeks. Blood samples were drawn and analysed at selected extraction times. The bone marker development pre-castration showed age-related and cycle-related changes. Osteocalcin showed definite increased concentrations, at the age of 9-13 months. If 10 months were seen as a late prepubal stage (Tanner stage) in the minipig, osteocalcin reacts more slowly in minipigs as it does in humans. Assuming that female minipigs in the present study can be compared with female humans during puberty, the present study shows that osteocalcin concentrations are still high at late puberty, unlike those in humans, which are high at midpuberty. Crosslaps increased up until the age of 10 months and then showed a constant decrease in concentrations. This would be the equivalent reaction of resorption markers in humans. Osteocalcin concentrations increased with an increase in estradiol concentrations, so estradiol stimulates bone formation in miniature pigs. The resorption marker serum crosslaps also showed cyclic fluctuations. High crosslaps concentrations were found in the estrus cycle stage or late follicular cycle stage; whereas low crosslaps were found in the luteal phase. As was often the case in other studies, the effect of a calcium reduced diet was not evident between the control and second control group. Resorption and formation markers showed changes post-castration in the OVX group, which shows that this is a calcium diet that can be used in further studies where induced osteopenia is required. Osteocalcin showed a definite concentration increase 4 weeks after castration. Serum crosslaps increased 2 weeks post operation. These increased concentrations were not significant, which could be due to the small animal numbers included in this study. Both markers reacted within a short time after ovariohysterectomy, which is a useful aspect for further osteoporosis research. This study portrayed the usefulness of the minipig as an animal model, not only for further studies on postmenopausal osteoporosis, but also verified the use of osteocalcin and serum crosslaps as biochemical parameters of bone metabolism in this species, to have age-related and cycle-related fluctuations, which should be considered in further studies.

In der vorliegenden Studie wurde erstmals der knochenprotektive Effekt von Seltenen Erden im Osteoporosemodell der ovariektomierten Ratte untersucht. Bei den Seltenen Erden handelt es sich um 17 chemische Elemente, die zur dritten Nebengruppe des Periodensystems gehören. Die Studie wurde als Fütterungsversuch an 60 weiblichen Wistar Han Ratten über einen Zeitraum von 6 Monaten durchgeführt. Die Versuchstiere wurden in eine scheinoperierte Postivkontrollgruppe (SHAM), eine ovariektomierte, aber nicht therapierte Negativkontrollgruppe (OVX) und in vier ovariektomierte Therapiegruppen eingeteilt. Von den vier Therapiegruppen erhielten zwei Gruppen reines Lanthancarbonat (1740 mg/kg Futter) und zwei Gruppen eine Seltene-Erd-Citrat Mischung (8000 mg/kg Futter). Zudem wurde jeweils eine der beiden Wirkstoffgruppen mit zusätzlich 1500 I.E. Vitamin D supplementiert. Jede Gruppe umfasste 10 Tiere. Als Parameter für die Knochenformation wurde Osteocalcin im Serum und als Parameter für die Knochenresorption wurden die Collagencrosslinks Pyridinolin und Desoxypyridinolin im Urin bestimmt. Die Probenahme erfolgte dabei einmal pro Monat. Um die direkte Wirkung der Seltenen Erden auf den Knochen zu untersuchen, wurde post mortem die Knochenmasse, die Knochenlänge und der Knochenaschegehalt mit seinem Gehalt an Calcium, Phosphor und Magnesium bestimmt. Die Dichte und Architektur des Knochens wurden mit Hilfe der Knochendichtemessung mittels Peripherer Quantitativer Computertomographie und Microcomputertomographie gemessen. Um mögliche Veränderungen der Organe durch die Applikation der Seltenen Erden in der gewählten Dosierung beurteilen zu können, wurden post mortem die Organgewichte von den Kreislauforganen Herz und Lunge, sowie von den Stoffwechselorganen Niere und Leber bestimmt. Außerdem wurde die Calcium- und Phosphorkonzentration der Herzen und der Lebern bestimmt. Die Ergebnisse der Studie zeigen bei den meisten gemessenen Parametern, dass die eingesetzten Seltenen Erden über einen knochenprotektiven Effekt verfügen. Ein zusätzlicher additiver Effekt von Vitamin D bestand dabei jedoch nicht. So konnte in jeder der Therapiegruppen der durch die Ovariektomie entgleiste Knochenstoffwechsel positiv beeinflusst werden. Ein antiresorptiver Effekt und eine Aktivierung der Osteoblasten konnten nachgewiesen werden. Dies führte desweiteren zu einer signifikanten Erhöhung des Calciumgehaltes der Knochenasche. Darüberhinausgehend wurde auch die Knochendichte positiv beeinflusst. Es kann also zusammenfassend festgestellt werden, dass die Seltenen Erden in dieser Studie knochenprotektive Eigenschaften gezeigt haben. Somit ist zu überlegen, ob Seltene Erden eine Alternative zu den bisher eingesetzten Prophylaktika und Therapeutika in der Osteoporose darstellen könnten.

Zielsetzung und Fragestellung: Bei der Behandlung von Knochendefekten wird dem Tissue Engineering großes Potential zugesprochen. In der vorliegenden Untersuchung wurden humane Mesenchymale Stammzellen (hMSC) in vitro vermehrt und unter osteogener Stimulation auf einer bereits klinisch zur Knochendefektfüllung zugelassenen Leitschiene kultiviert. Ziel der Arbeit war neben der Etablierung des Modells zunächst die qualitative Beurteilung des Zellwachstums über Zeiträume von 2, 4 und 6 Wochen. Insbesondere aber sollte der immunhistochemische Nachweis von Zelldifferenzierung und Matrixbildung im dreidimensionalen System im Vergleich zur zweidimensionalen Kultur über einen Zeitraum von 2 Wochen erfolgen, und damit die Untersuchung des Einflusses der Dreidimensionalität der gewählten Leitschiene. Material und Methoden: Die Vermehrung der hMSC (Fa. Poietics) erfolgte in DMEM unter Zugabe von FBS, L-Glutamin und Antibiotika. Die zylinderförmigen Leitschienen (Tutobone, Fa. Tutogen Medical, d= 9 mm, h= 3 mm) wurden mit jeweils 1,6 Mio. Zellen besiedelt. Die Kultivierung erfolgte im Bioreaktor für 2, 4 und 6 Wochen bei kontinuierlicher Mediumversorgung (3,3 ml/h). Zur osteogenen Stimulation wurde Dexamethason, Ascorbinsäure-2-Phosphat und beta-Glycerophosphat zugesetzt. Für die 2-D-Vergleichsgruppen wurde ein Teil der Ausgangszellen mit, ein weiterer Teil ohne osteogene Stimulation für 2 Wochen fortgeführt. Nach 2, 4 und 6 Wochen erfolgte die auflichtmikroskopische, histologische und immunhistochemische Auswertung aller Präparate. Alle Versuche wurden dreifach durchgeführt, die Kulturen über 4 Wochen einfach. Ergebnisse: Innerhalb der Leitschienen konnte in allen Versuchszeiträumen homogenes, dreidimensionales Zellwachstum sowie deutliche Matrixbildung gezeigt werden. Die immunhistochemischen Nachweise für Prokollagen I, Kollagen I und IV, Osteocalcin, Osteonectin, und Versican waren in den 3-D-Präparaten in allen Zeiträumen deutlich positiv, die Nachweise für Alkalische Phosphatase und Decorin negativ. Im Vergleich zu den 3-D-Kulturen war in der stimulierten 2-D-Kultur die Markierung von Osteocalcin deutlich schwächer ausgeprägt. Ohne osteogene Stimulation konnten in den 2-D-Kulturen positive Nachweise für Kollagen I, Kollagen IV, Osteonectin, Prokollagen I und Versican gefunden werden, keine Nachweise für Alkalische Phosphatase, Decorin und Osteocalcin. Schlussfolgerungen: 1. Die dreidimensionale Kultivierung von humanen MSC in vitro in Verbindung mit der gewählten Leitschiene und unter kontinuierlicher Mediumversorgung ist über Zeiträume bis zu 6 Wochen möglich. 2. In allen Versuchszeiträumen führte dies bereits nach qualitativen Gesichtspunkten zu ausgeprägtem dreidimensionalem Zellwachstum. 3. Als Zeichen osteogener Differenzierung fällt der Nachweis des osteoblastentypischen Markers Osteocalcin in den 3-D-Kulturen im Vergleich zu den 2-D-Kulturen deutlich positiv aus. Dreidimensionales Zellwachstum in vitro stellte unter den gewählten Bedingungen einen zusätzlichen Stimulus für die osteogene Differerenzierung dar. 4. Alkalische Phosphatase, Decorin, Prokollagen I, Kollagen I und IV, Osteonectin und Versican eigneten sich in der vorliegenden Untersuchung nicht als spezifische Marker der osteoblastären Kaskade.

Mit zunehmendem Wissen über die Komplexität der Osteogenese wurde die Aussagekraft einzelner osteoblasten-assoziierter Marker in den letzten Jahren immer mehr in Frage gestellt. Denn der Nachweis einzelner Marker erlaubt weder eine eindeutige Identifikation undifferenzierter hMSC noch eine Abgrenzung von hMSC zu anderen Reifungsstufen der osteoblastären Kaskade. Das Ziel dieser Untersuchung war es daher, über die Erstellung eines immunzytochemischen Färbeprofils mehrerer Marker gleichzeitig, undifferenzierte hMSC eindeutig zu identifizieren und sie gegenüber hOB und evtl. weiteren Differenzierungsstufen der osteoblastären Kaskade abzugrenzen. Durch die Erstellung eines immunzytochemischen Färbeprofils ist es möglich, heterogene Zellpopulationen auf Einzelzellniveau zu charakterisieren und sie voneinander zu unterscheiden. Diese Untersuchung stellt einen sehr erfolgversprechenden Ansatz dar, undifferenzierte humane mesenchymale Stammzellen (hMSC) zu identifizieren und sie von Zellen der osteoblastären Differenzierungskaskade sowie anderen Zelltypen abgrenzen zu können. Insgesamt konnte in dieser Arbeit gezeigt werden, dass humane MSC und humane Osteoblasten jeweils spezifische Färbeprofile aufweisen, die eine eindeutige Diskriminierung der beiden Zellpopulationen erlauben. Für eine spezifische Unterscheidung auf Einzelzellnineau ist eine intensive Suche nach spezifischen Markern oder die Kombination mehrerer Marker notwendig. Von den in dieser Arbeit ausgewählten Proteinen ergaben Bone Sialoprotein, Osteocalcin, Decorin sowie Kollagen-IV und Kollagen-X unterschiedliche Färbemuster. Kollagen-IV und –X waren besonders in hMSC positiv, weswegen sie sich für eine Erkennung unreifer osteoblastärer Zellen anbieten. Bone Sialoprotein, Osteocalcin und Decorin eignen sich dagegen für einen Nachweis reifer osteoblastärer Zellen, denn sie waren nur in hOB positiv. Osteocalcin und Decorin erlaubten außerdem eine Abgrenzung differenzierter hOB. Die Proteine Versican und Matrixmetalloproteinase-2 erscheinen darüber hinaus für eine Unterscheidung von osteoblastären und fibroblastären Zellen nützlich zu sein. Die klassischen osteoblastären Marker alkalische Phosphatase, Kollagen-I, Osteopontin oder Osteonectin waren für eine Unterscheidung von hMSC und hOB nicht geeignet, da sie in beiden Zellpopulationen gleiche Ergebnisse lieferten. Insbesondere der Wert der alkalische Phosphatase als immunzytochemischer Marker der osteoblastären Kaskade wird in dieser Untersuchung in Frage gestellt. Eine osteogene Stimulation von hMSC mit Dexamethason, b-Glyzerophosphat und Askorbinsäure bewirkte eine deutliche Veränderung der Morphologie, der Wachstumseigenschaften und des Färbeprofils. Allerdings konnte durch eine osteogene Stimulation kein immunzytochemischer Phänotyp von hMSC induziert werden, welcher identisch mit dem der hOB war. Daher ist es unwahrscheinlich, dass eine Stimulation in vitro mit den oben aufgeführten Zusätzen die komplizierten Verhältnisse der Osteogenese in vivo nachahmen kann.

Two human stromal cell lines were established previously from bone marrow-derived primary long-term cultures by immortalization using the SV40 large T antigen and cellular cloning. After irradiation, the fibroblast-like cell lines L87/4 and L88/5 support hematopoietic differentiation of allogeneic cord blood cells in vitro. The stromal cells do not express CD34 and CD50, but some adhesion molecules and integrins, such as CD44, CD54 and CD58. Their expression profiles on RNA and protein levels are suggestive of their osteogenic potency. The quality and quantity of osteocalcin and osteopontin protein expression depended on the culture conditions. Expression of the osteogenic markers increased over time in culture, especially in cells growing in clusters. The stromal cells also expressed collagens I and V, but did not show any expression of collagens II and III. The potentially osteoblastic stromal cells were transplanted into NOD/SCID recipient mice by intravenous injection and were found in various mesenchymal organs up to 10 weeks after transplantation. Osteocalcin-positive human stromal cells could be detected in the bone marrow, thymus, liver, brain and gut of the recipient animals. In summary, there is evidence that human bone-marrow-derived stromal cells have to be considered mesenchymal progenitors, persistently expressing osteogenic markers in vitro and in vivo. Copyright (C) 2001 S, Karger AG, Basel.