How does estrogen protect bones?

Tokyo-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 are at a high risk of developing osteoporosis, which may be due to the loss of estrogen that occurs after menopause. While studies have linked estrogen levels to bone health, the exact details of this connection are not entirely clear. Researchers at Tokyo Medical and Dental University (TMDU) describe a new molecular link between estrogen and bone aging, which may eventually lead to new strategies to treat postmenopausal osteoporosis.

Bone is a complex tissue, consisting of a matrix of proteins and minerals that give it the flexibility and strength to support body movement. Bone also contains several types of specialized cells, including osteocytes, that help to maintain this matrix. Over a person's lifetime, many factors can affect how healthy bone structure is maintained. One of these factors is the female sex hormone, estrogen.

"Over the last few decades, we've learned that estrogen plays an important role in maintaining a functional bone matrix," corresponding authors Tomoki Nakashima and Hiroshi Takayanagi explain. "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."

Sema3A does indeed appear to be linked to estrogen: the researchers found that blood serum levels of the protein decrease in premenopausal women as they get older -- and drop even further once women reach menopause. But how, at the biological level, are estrogen and Sema3A related? And what is Sema3A doing in bone tissue?

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