Scientists Uncover Mechanism Of Post-Menopausal Bone Loss

Scientists in Japan have found that a protein known as Sema3A interacts with estrogen signaling to maintain bone health.

AsianScientist (Apr. 2, 2019) – In a study published in the journal Cell Metabolism, a research group in Japan has identified a molecular mechanism by which estrogen impacts bone health.

Osteoporosis is a condition in which bones become weak and prone to fractures. Fractures typically occur in the wrist, spine or hip, and can often lead to permanently impaired mobility. Women over 50 years of age are at a high risk of developing osteoporosis, or the loss of bone density. While studies have linked estrogen levels to bone health, the exact details of this connection are not entirely clear.

In the present study, researchers at the Tokyo Medical and Dental University (TMDU), Japan, described a molecular link between estrogen and bone aging.

“Over the last few decades, we’ve learned that estrogen plays an important role in maintaining a functional bone matrix,” said corresponding author Professor Hiroshi Takayanagi of the University of Tokyo. “Exactly how estrogen does this, though, is not fully understood. Our laboratory recently discovered that bone matrix is maintained by a protein called Sema3A, which is secreted by osteocytes. This led us to suspect that there might be a mechanistic relationship between estrogen and Sema3A.”

The researchers found that blood serum levels of Sema3A decrease in premenopausal women as they get older and drop even further once women reach menopause. In mice whose ovaries had been removed, the bone-specific deletion of Sema3A also prevented intravenous estrogen from sustaining bone density. Furthermore, the team demonstrated that Sema3A sets off a chain of signaling events that promote the survival of osteocytes—bone precursors—in these mice.

“We believe that as women lose estrogen with age and Sema3A levels drop off, osteocytes begin to die and bone loses the ability to maintain its supportive structure,” said the researchers.

The scientists hope that the discovery of Sema3A as a major player in bone health may lead to the discovery of new therapeutic approaches to treating osteoporosis.

The article can be found at: Hayashi et al. (2019) Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and Counteracts Bone Aging.


Source: Tokyo Medical and Dental University; Photo: Shutterstock.
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