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胶质细胞成熟因子-β 缺乏通过重塑肌动蛋白网络抑制骨髓间充质干细胞成脂分化来预防雌激素缺乏诱导的骨丢失。

Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells.

机构信息

Department of Orthopedics, Minhang Hospital, Fudan University, Shanghai, PR China.

Department of Rehabilitation, Tongji Hospital Affiliated to Tongji University, Tongji University School of medicine, Shanghai, PR China.

出版信息

Cell Death Dis. 2024 Nov 14;15(11):829. doi: 10.1038/s41419-024-07234-z.

DOI:10.1038/s41419-024-07234-z
PMID:39543090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11564563/
Abstract

An imbalance between the adipogenesis and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is considered the basic pathogenesis of osteoporosis. Although actin cytoskeleton remodelling plays a crucial role in the differentiation of BMSCs, the role of actin cytoskeleton remodelling in the adipogenesis of BMSCs and postmenopausal osteoporosis (PMOP) has remained elusive. Glia maturation factor-beta (GMFB) has a unique role in remodelling the polymerization/depolymerization cycles of actin. We observed that GMFB expression was increased in bone tissue from both ovariectomized (OVX) rats and PMOP patients. GMFB knockout inhibited the accumulation of bone marrow adipocytes and increased bone mass in the OVX rat model. The inhibition of adipocyte differentiation in GMFB knockout BMSCs was mediated via actin cytoskeleton remodelling and the Ca-calcineurin-NFATc2 axis. Furthermore, we found that GMFB shRNA treatment in vivo had favourable effects on osteoporosis induced by OVX. Together, these findings suggest a pathological association of the GMFB with PMOP and highlight the potential of the GMFB as a therapeutic target for osteoporosis patients.

摘要

骨髓间充质干细胞（BMSCs）成脂和成骨的失衡被认为是骨质疏松症的基本发病机制。尽管细胞骨架重构在 BMSCs 的分化中起着至关重要的作用，但细胞骨架重构在 BMSCs 的成脂作用和绝经后骨质疏松症（PMOP）中的作用仍不清楚。神经胶质细胞成熟因子-β（GMFB）在肌动蛋白聚合/解聚循环的重构中具有独特的作用。我们观察到 GMFB 在去卵巢（OVX）大鼠和 PMOP 患者的骨组织中表达增加。GMFB 敲除抑制 OVX 大鼠模型中骨髓脂肪细胞的积累并增加骨量。GMFB 敲除 BMSCs 中脂肪细胞分化的抑制是通过肌动蛋白细胞骨架重构和 Ca-钙调神经磷酸酶-NFATc2 轴介导的。此外，我们发现体内 GMFB shRNA 治疗对 OVX 诱导的骨质疏松症有良好的效果。总之，这些发现表明 GMFB 与 PMOP 存在病理关联，并强调了 GMFB 作为骨质疏松症患者治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/06dcb61a0acd/41419_2024_7234_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/7920527374e2/41419_2024_7234_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/a2d6f58b80a9/41419_2024_7234_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/06dcb61a0acd/41419_2024_7234_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/3cd550e66ac3/41419_2024_7234_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/0aeb4dbd8b2f/41419_2024_7234_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/7920527374e2/41419_2024_7234_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/0df7f8e499cc/41419_2024_7234_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/a2d6f58b80a9/41419_2024_7234_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fad/11564563/06dcb61a0acd/41419_2024_7234_Fig8_HTML.jpg

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