Unlocking a key behind why our bones get weaker as we age

Magnified image of a bone with osteoporosis. Photo Courtesy Sciencephoto.com

Getting older brings with it a mixed bag of items. If you are lucky you can get wiser. If you are not so lucky you can get osteoporosis. But while scientists don’t know how to make you wiser, they have gained some new insights into what makes bones weak and so they might be able to help with the osteoporosis.

Around 200 million people worldwide suffer from osteoporosis, a disease that causes bones to become so brittle that in extreme cases even coughing can lead to a fracture.

Scientists have known for some time that the cells that form the building blocks of our skeletons are found in the bone marrow. They are called mesenchymal stem cells (MSCs) and they have the ability to turn into a number of different kinds of cells, including bone or fat. The keys to deciding which direction the MSCs take are things called epigenetic factors, these basically control which genes are switched on or off and in what order. Now researchers from the UCLA School of Dentistry have identified an enzyme that plays a critical role in that process.

The team found that when the enzyme KDM4B is missing in MSCs those cells are more likely to become fat cells rather than bone cells. Over time that leads to weaker bones and more fractures.

In a news release Dr. Cun-Yu Wang, the lead researcher, said: “We know that bone loss comes with age, but the mechanisms behind extreme cases such as osteoporosis have, up until recently, been very vague.”

To see if they were on the right track the team created a mouse model that lacked KDM4B. Just as they predicted the MSCs in the mouse created more fat than bone, leading to weaker skeletons.

They also looked at mice who were placed on a high fat diet – something known to increase bone loss and weaker bones in people – and found that the diet seemed to reduce KDM4B which in turn produced weaker bones.

In the news release Dr. Paul Krebsbach, Dean of the UCLA School of Dentistry, said the implications for the research are enormous. “The work of Dr. Wang, his lab members and collaborators provides new molecular insight into the changes associated with skeletal aging. These findings are an important step towards what may lead to more effective treatment for the millions of people who suffer from bone loss and osteoporosis.”

The study is published in the journal Cell Stem Cell.

One thought on “Unlocking a key behind why our bones get weaker as we age

  1. Estrogen control the menstrual cycle of female and is important for childbearing. Estrogen has other functions to keep cholesterol in control and protect bone health for women and men. Therefore, estrogen plays important physiological role to prevent bone resorption. In adult skeleton, estrogen slows the rate of bone remodeling and maintain bone formation and resorption. The body is consistently resorbing old bone and creating new bone cells to keep bone health. The homeostasis in bone cells is essential to make a balance for both old and new bone cells. Mesenchyma stem cells (MSCs) are adult stem cells which can differentiate into chondrocytes, adipocytes, ostoeclasts, osteoblasts, myocytes and hepatocytes. In female, the rise and drop of estrogen levels during menstrual cycle produce an impact on bone health. Estrogen has directs effects on osteocytes, osteoclasts and osteoblasts lead to inhibit bone resorption and maintain bone formation. Previous investigation showed that all osteoblasts, osteocytes and osteoclasts express estrogen receptors. Evidence proved that bone cells produce two diverse types of estrogen receptors. The binding of ligand to certain receptor type may activate many targeted genes expression but not for the other. Therefore, the existence of both low and high affinity estrogen receptors response to high and low concentration of estrogen respectively. Research findings indicated that KDM4B is a co-regulator of estrogen receptor signaling cascade and plays a key regulator for estrogen receptor -targeted genes transcription and expression to control the estrogen-dependent phenotype. MSCs requires estrogen to interact with cell-surface receptor to produce signaling for growth, differentiation and functioning. Therefore, MSCs with deleted KDM4B gene may cripple the signaling cascade from functioning and resulted stem cells take turned into adipocytes. Osteoblasts are belived to derive from MSCs, that originated in bone marrow. They maintain the bone formation in response to estrogen. Whereas, osteoclasts are hematopoitic cells which play important roles in bone remodeling and resorption. The deficiency of estrogen levels cause the increase of the number of osteoclasts but decrease osteoblasts resulting in overall bone resorption. Thus, estrogen affects bone indirectly through cytokines and local growth factors. During the estrogen-replete state may enhance osteoclasts apoptosis via increased production of TGF-β. The absence of estrogen may trigger T cells release IL-1, IL-6 and TNF-α to promote recruitment of osteoclasts for differentiation and survive longer. Evidence proved that estrogen inhibits the secretion of IL-6 which contributes recruitment of osteoclasts from monocyte cell line and lead to osteoporosis.

    Women are more at risk of developing osteoporosis than men. The regulation of estrogen in menstrual cycles in female and a fall of hormones in menopause cause a rapid decrease in bone density. Whereas men has constant level of estrogen and gradually fall during aging.

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