osteoblasts

Proteins causing daytime sleepiness tied to bone formation, providing target for osteoporosis

Orexin proteins, which are blamed for spontaneous daytime sleepiness, also play a crucial role in bone formation, according to findings by UT Southwestern Medical Center researchers. The findings could potentially give rise to new treatments for osteoporosis, the researchers say.

Orexins are a type of protein used by nerve cells to communicate with each other. Since their discovery at UT Southwestern more than 15 years ago, they have been found to regulate a number of behaviors, including arousal, appetite, reward, energy expenditure, and wakefulness. Orexin deficiency, for example, causes narcolepsy – spontaneous daytime sleepiness. Thus, orexin antagonists are promising treatments for insomnia, some of which have been tested in Phase III clinical trials.

UT Southwestern researchers, working with colleagues in Japan, now have found that mice lacking orexins also have very thin and fragile bones that break easily because they have fewer cells called osteoblasts, which are responsible for building bones.

“Osteoporosis is highly prevalent, especially among post-menopausal women. We are hoping that we might be able to take advantage of the already available orexin-targeting small molecules to potentially treat osteoporosis,” said Dr. Yihong Wan, Assistant Professor of Pharmacology, the Virginia Murchison Linthicum Scholar in Medical Research, and senior author for the study, published in the journal Cell Metabolism.

Osteoporosis, the most common type of bone disease in which bones become fragile and susceptible to fracture, affects more than 10 million Americans. The disease, which disproportionately affects seniors and women, leads to more than 1.5 million fractures and some 40,000 deaths annually. In addition, the negative effects impact productivity, mental health, and quality of life. One in five people with hip fractures, for example, end up in nursing homes.

Orexins seem to play a dual role in the process: they both promote and block bone formation. On the bones themselves, orexins interact with another protein, orexin receptor 1 (OX1R), which decreases the levels of the hunger hormone ghrelin. This slows down the production of new osteoblasts and, therefore, blocks bone formation locally. At the same time, orexins interact with orexin receptor 2 (OX2R) in the brain. In this case, the interaction reduces the circulating levels of leptin, a hormone known to decrease bone mass, and thereby promotes bone formation. Therefore, osteoporosis prevention and treatment may be achieved by either inhibiting OX1R or activating OX2R.

“We were very intrigued by this yin-yang-style dual regulation,” said Dr. Wan, a member of the Cecil H. and Ida Green Center for Reproductive Biology Sciences and UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center. “It is remarkable that orexins manage to regulate bone formation by using two different receptors located in two different tissues.”

The central nervous system regulation through OX2R, and therefore promotion of bone formation, was actually dominant over regulation through OX1R. So when the group examined mice lacking both OX1R and OX2R, they had very fragile bones with decreased bone formation. Similarly, when they assessed mice that expressed high levels of orexins, those mice had increased numbers of osteoblasts and enhanced bone formation.

Vera Malheiro - ‘Human osteoblasts in culture’

Microscopy images of human bone cells (osteoblasts) stained with GIEMSA allowing to visualise the cells nucleus, nucleoli and cytoplasm. My PhD project is related to the evaluation of biocompatibility of ferritic stainless steels. In order to perform biocompatibility studies is crucial to understand the types of cells that are used for them. Staining cells allows for the observation of the cell morphology, and this is the most direct technique to identify cell type and screen if there is any problems with them. These particular pictures were taken in the context of a baseline experiment where I was studying the characteristics of foetal human osteoblasts (FHOBS) cells for better comprehension of their biology in vitro. The goal was to access if FHOBS were a valid in vitro model to evaluate the biocompatibility of metallic biomaterials to be used in bone implants. The image has been treated in Photoshop for color change and quality improvement.

#Cannabidiol, a Major Non-Psychotrophic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in #Osteoblasts.

Abstract

“#Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort.

Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures.

The maximal load and work-to-failure, but not the stiffness, of femora from rats given a mixture of CBD and THC for 8 weeks were markedly increased by CBD.

This effect is not shared by Δ9 -tetrahydrocannabinol (THC, the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks post fracture followed by attenuation of the CBD effect at 8 weeks.

Using μCT, the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC.

By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier Transform Infrared Spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus.

Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes.

This article is protected by copyright. All rights reserved.”

#PureMedicinals #PureReleaf #cannabisismedicine #cannabisscience
#CBD #THC #cannabis #mmj #organic #nonGMO #tincture #tinctures #balm #balms #topical #topicals #healing #herbalism #alchemy #love #health #wellness #wholeflower #liquidextract #labtested #realmedicine #NaturallyMysticOrganics

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CURRENTLY: #Osteoblasts ARE HERE BLASTING US AWAY #spacefortytwo (at space forty-two)

Bone Health

Many people believe that the best thing for building strong and healthy bones is to drink lots of cow’s milk for calcium. This is far from the truth. Creating a load on the bone that produces a mechanical stimulus is what actually leads greater bone density. Here’s why…

We have 3 types of bones cells:

  1. Osteoclasts - responsible for reabsorbing/taking away old bone cells
  2. Osteoblasts - responsible for laying down new bone
  3. Osteocytes - are mature osteoblasts, make up the compact cortical bone

In the picture below, you can see the the remodeling process taking place.

Changes in Bone Mass with Aging

We typically reach our peak bone mass somewhere in our early 20s, which we can maintain up until around 50 years of age. Males also tend to have a higher peak bone mass than women.

After the age of 50, males will see a gradual decrease where as females experience a more dramatic decline (thanks to menopause, and hence why women are at a greater risk of developing osteoporosis). Unfortunately, everyone will have a decline as they age, but if you are more active when you are young, you can achieve a higher bone mass, creating a safety buffer. If you start with a higher bone mass, you won’t reach dangerously low levels.

Loading vs. No Loading

Below you can see what happens to bone undergoing (a) substantial loading and (b) no loading.Bone that experience loading will maintain thickness due to stress stimulating new bone to be laid down. Bone that does not experience any loading will have bone resorption happening from the inside.

Where Does The Stress On Bone Come From?

Most of the strain put on bone comes from muscle pulling on the bone to create movement. This is why weight training/weight bearing exercise is a great stimulus for increasing bone density. 

Frost’s Mechanostat Theory

How does the bone know to adapt to physical strain? Bone thickness/strength is controlled by a mechanostat - your bone is trying to maintain an optimal strength within a narrow range, so it will make changes in response to stress. In order for the bone to make changes and lay down new bone (modeling), the load on the bone will have to land in the “Overload Zone.” If you are in the “Pathological Overload Zone,” you risk injury. In the “Trivial Loading Zone,” the bone is not experience enough stress and resorption occurs. 

How A Mechanical Stress Stimulates Bone Cells

  1. Bending of bone causes a pressure gradient.
  2. Sheer stress causes a biochemical response in osteocytes.
  3. Biochemical signaling to adjacent cells.
  4. Osteoblasts lay down new bone.

When the mechanical stress is applied, the bone experiences some bending, moving the fluid within the bone - the external stress is transformed into an internal stress. The fluid moves around the osteocytes, causing sheer stress against the surface of the cells. Osteosytes pass signal from one to the other, eventually getting to the specialized cells near the surface (the bone lining cells), stimulating the laying down of new bone.

When human mesenchymal stem cells treated with SR2595, osteoblast formation increased

Scripps Research Institute says that scientists have identified a new therapeutic approach that, while still preliminary, could promote the development of new bone-forming cells in patients suffering from bone loss. The scientists knew that a partial loss of PPARy in a genetically modified mouse model led to increased bone formation. To see if they could mimic that effect using a drug candidate, the researchers combined a variety of structural biology approaches to rationally design a new compound that could repress the biological activity of PPARy. The results showed that when human mesenchymal stem cells were treated with the new compound, which they called SR2595 (SR=Scripps Research), there was a statistically significant increase in osteoblast formation, a cell type known to form bone. “These findings demonstrate for the first time a new therapeutic application for drugs targeting PPARy, which has been the focus of efforts to develop insulin sensitizers to treat type 2 diabetes,” said Patrick Griffin, chair of the Department of Molecular Therapeutics and director of the Translational Research Institute at Scripps Florida. “We have already demonstrated SR2595 has suitable properties for testing in mice; the next step is to perform an in-depth analysis of the drug’s efficacy in animal models of bone loss, aging, obesity and diabetes.”

Citations

http://www.scripps.edu/news/press/2015/20150612griffin.html

http://www.nature.com/ncomms/2015/150612/ncomms8443/full/ncomms8443.html Scripps Research Institute. “Potential new treatment for osteoporosis.” ScienceDaily. ScienceDaily, 12 June 2015. . https://thehealtharchive.wordpress.com/2015/06/16/when-human-mesenchymal-stem-cells-treated-with-sr2595-osteoblast-formation-increased/

Black rice extract is a potentially useful ingredient to protect against age related osteoporosis and diet induced obesity.

PMID:  Food Funct. 2015 Jan ;6(1):265-75. Epub 2014 Nov 27. PMID: 25428526 Abstract Title:  Black rice (Oryza sativa L.) extracts induce osteoblast differentiation and protect against bone loss in ovariectomized rats. Abstract:  Osteoporosis, an age associated skeletal disease, exhibits increased adipogenesis at the expense of osteogenesis from common osteoporotic bone marrow cells. In this study, black rice (Oryza sativa L.) extracts (BRE) were identified as osteogenic inducers. BRE stimulated the alkaline phosphatase (ALP) activity in both C3H10T1/2 and primary bone marrow cells. Similarly, BRE increased mRNA expression of ALP and osterix. Oral administration of BRE in OVX rats prevented decreases in bone density and strength. By contrast, BRE inhibited adipocyte differentiation of mesenchymal C3H10T1/2 cells and prevented increases in body weight and fat mass in high fat diet fed obese mice, further suggesting the dual effects of BRE on anti-adipogenesis and pro-osteogenesis. UPLC analysis identified cyanidin-3-O-glucoside and peonidin-3-O-glucoside as main anti-adipogenic effectors but not for pro-osteogenic induction. In mechanism studies, BRE selectively stimulated Wnt-driven luciferase activities. BRE treatment also induced Wnt-specific target genes such as Axin2, WISP2, and Cyclin D1. Taken together, these data suggest that BRE is a potentially useful ingredient to protect against age related osteoporosis and diet induced obesity. http://j.mp/1JaIZJi

The investigation of the effect of varying cross-link densities on mineralisation on MT3T3-E1 pre-osteoblasts.

The investigation of the effect of varying cross-link densities on mineralisation on MT3T3-E1 pre-osteoblasts. Project description I need an introduction and background in this topic: The investigation of the effect of varying cross-link densities on mineralisation on MT3T3-E1 pre-osteoblasts.

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When human mesenchymal stem cells treated with SR2595, osteoblast formation increased

Scripps Research Institute says that scientists have identified a new therapeutic approach that, while still preliminary, could promote the development of new bone-forming cells in patients suffering from bone loss. The scientists knew that a partial loss of PPARy in a genetically modified mouse model led to increased bone formation. To see if they could mimic that effect using a drug candidate, the researchers combined a variety of structural biology approaches to rationally design a new compound that could repress the biological activity of PPARy. The results showed that when human mesenchymal stem cells were treated with the new compound, which they called SR2595 (SR=Scripps Research), there was a statistically significant increase in osteoblast formation, a cell type known to form bone. “These findings demonstrate for the first time a new therapeutic application for drugs targeting PPARy, which has been the focus of efforts to develop insulin sensitizers to treat type 2 diabetes,” said Patrick Griffin, chair of the Department of Molecular Therapeutics and director of the Translational Research Institute at Scripps Florida. “We have already demonstrated SR2595 has suitable properties for testing in mice; the next step is to perform an in-depth analysis of the drug’s efficacy in animal models of bone loss, aging, obesity and diabetes.”

Citations

http://www.scripps.edu/news/press/2015/20150612griffin.html

http://www.nature.com/ncomms/2015/150612/ncomms8443/full/ncomms8443.html Scripps Research Institute. “Potential new treatment for osteoporosis.” ScienceDaily. ScienceDaily, 12 June 2015. . https://thehealtharchive.wordpress.com/2015/06/16/when-human-mesenchymal-stem-cells-treated-with-sr2595-osteoblast-formation-increased/