Chinese scholars have made progress in the study of the mechanism of osteoporosis

Figure Diagram of the mode of action of skin keratinocytes secreting cystatin-A (Csta) in regulating bone metabolism

With the support of the National Natural Science Foundation of China (grant numbers: 82172507, 81700783, 81991511), Huang Bin's team at Southern Medical University has made progress
in the mechanism of osteoporosis 。 The research results, titled "Skin chronological aging drives age-related bone loss via secretion of cystatin-A," were published on October 6, 2022 in Nature In
the journal Nature Aging.
Links to papers: _istranslated="1">.

Osteoporosis is a common degenerative disease of the bone, which is mainly manifested by osteopenia, destruction of bone microstructure, and increased
bone fragility.
Osteoporotic fractures can cause disability and death of patients, seriously endangering human life and health
.
There are currently about 90 million osteoporosis patients in China, mainly distributed in postmenopausal women and the elderly
.
Clinical studies have found that many elderly women with osteoporosis have changes in skin thickness, suggesting an association
between skin aging and osteoporosis.

The team found that the thickness of the epidermis in aged mice was proportional to bone mass; Induce premature aging in the epidermis of young mice, which can lead to osteopenia
.
Cystatin-A (Csta), secreted by epidermal keratinocytes, is abundant in bone marrow and can regulate the proliferation and differentiation of osteoblasts and osteoclasts; When the mouse specifically knocked out keratinocyte Csta, its epidermis became thin and its bone mass decreased
.
Molecular mechanism studies have found that after skin-derived Csta enters the bone, it binds to the Rack1 receptor in osteogenic and osteoclastic precursor cells and activates Src kinase, thereby promoting osteoblastic proliferation, inhibiting osteoclast differentiation, and maintaining bone metabolic balance
.
The team also found through drug screening that calcipotriene can significantly stimulate epidermal keratinocyte expression and secretion of Csta, and topical calcipotriene can effectively alleviate osteoporosis progression in elderly mice (Figure).

This study not only reveals the molecular mechanism of skin aging to promote osteoporosis, provides a potential target for the prevention and treatment of osteoporosis, but also enriches the theoretical knowledge
of extraosseous organs regulating bone metabolism.