破骨细胞
骨质疏松症
老年性骨质疏松症
内分泌学
成骨细胞
内科学
骨重建
激素
角质形成细胞
骨吸收
医学
化学
受体
生物化学
体外
作者
Wenquan Liang,Qingjing Chen,Shasha Cheng,Ruiming Wei,Yuejun Li,Chenfeng Yao,Zhicong Ouyang,Dawei Kang,Ajuan Chen,Zezheng Liu,Kai Li,Xiaochun Bai,Qingchu Li,Bin Huang
出处
期刊:Nature Aging
日期:2022-10-06
卷期号:2 (10): 906-922
被引量:11
标识
DOI:10.1038/s43587-022-00285-x
摘要
Although clinical evidence has indicated an association between skin atrophy and bone loss during aging, their causal relationship and the underlying mechanisms are unknown. Here we show that premature skin aging drives bone loss in mice. We further identify that cystatin-A (Csta), a keratinocyte-enriched secreted factor, mediates the effect of skin on bone. Keratinocyte-derived Csta binds the receptor for activated C-kinase 1 in osteoblast and osteoclast progenitors, thus promoting their proliferation but inhibiting osteoclast differentiation. Csta secretion decreases with skin aging in both mice and humans, thereby causing senile osteoporosis by differentially decreasing the numbers of osteoblasts and osteoclasts. In contrast, topical application of calcipotriol stimulates Csta production in the epidermis and alleviates osteoporosis. These results reveal a mode of endocrine regulation of bone metabolism in the skin, and identify Csta as an epidermally derived hormone linking skin aging to age-related bone loss. Enhancers of skin Csta levels could serve as a potential topical drug for treatment of senile osteoporosis. Skin thickness and bone density decrease with age; however, the interactions between skin and bone during aging are unclear. Here the authors show that cystatin-A is a skin-derived protein that decreases with age and causes age-related bone loss. Further, topical application of calcipotriol stimulates cystatin-A production in the skin and alleviates bone loss.
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