Oncostatin M receptor regulates osteoblast differentiation via extracellular signal-regulated kinase/autophagy signaling.
Oncostatin M receptor regulates osteoblast differentiation via extracellular signal-regulated kinase/autophagy signaling.
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DOI：
10.1186/s13287-022-02958-1
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发表时间：
2022-06-28
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
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肿瘤抑素M受体(OSMR)是肿瘤抑素M(OSM)的受体之一，已有研究表明OSM在破骨细胞形成和骨吸收中起促进作用。然而，OSMR是否以及如何影响成骨细胞的分化仍有待阐明。检测OSMR在成骨细胞和脂肪细胞分化过程中的表达水平。通过体外功能获得和功能丧失实验研究OSMR在分化过程中的作用。探讨了OSMR调控骨细胞分化的机制。最后，将OSMR沉默的骨髓基质细胞(BMSCs)移植到去卵巢小鼠的骨髓中，研究了OSMR在决定细胞命运和骨稳态中的作用。OSMR在骨髓基质前体细胞成骨和成脂分化过程中受到调控，在去卵巢小鼠干骺端表达增加。OSMR抑制成骨分化，促进成脂分化。机制研究表明，OSMR抑制细胞外信号调节激酶(ERK)和自噬信号。ERK抑制介导的自噬下调抑制了祖细胞的成骨分化。此外，ERK/自噬信号失活减弱了OsmR siRNA对成骨分化的刺激作用。此外，骨髓中OSMR沉默的BMSCs移植促进了成骨细胞的分化，减少了脂肪堆积和破骨细胞分化，从而减轻了去卵巢小鼠的骨量表型。我们的研究首次确定了OSMR通过ERK介导的自噬信号调节骨髓基质前体细胞成骨分化的直接作用。因此，OSMR通过对成骨细胞和破骨细胞的双重调节来促进骨骼的动态平衡。这也表明，OSMR可能是治疗骨质疏松症等代谢紊乱的潜在靶点。网上版载有补充材料，可在10.1186/s13287-022-02958-1查阅。
Oncostatin M receptor (OSMR), as one of the receptors for oncostatin M (OSM), has previously been shown to mediate the stimulatory role of OSM in osteoclastogenesis and bone resorption. However, it remains to be clarified whether and how OSMR affects the differentiation of osteoblasts. The expression level of OSMR during osteoblast and adipocyte differentiation was examined. The role of OSMR in the differentiation was investigated using in vitro gain-of-function and loss-of-function experiments. The mechanisms by which OSMR regulates bone cell differentiation were explored. Finally, in vivo function of OSMR in cell fate determination and bone homeostasis was studied after transplantation of OSMR-silenced bone marrow stromal cells (BMSCs) to the marrow of ovariectomized mice. OSMR was regulated during osteogenic and adipogenic differentiation of marrow stromal progenitor cells and increased in the metaphysis of ovariectomized mice. OSMR suppressed osteogenic differentiation and stimulated adipogenic differentiation of progenitor cells. Mechanistic investigations showed that OSMR inhibited extracellular signal-regulated kinase (ERK) and autophagy signaling. The downregulation of autophagy, which was mediated by ERK inhibition, suppressed osteogenic differentiation of progenitor cells. Additionally, inactivation of ERK/autophagy signaling attenuated the stimulation of osteogenic differentiation induced by Osmr siRNA. Furthermore, transplantation of BMSCs in which OSMR was silenced to the marrow of mice promoted osteoblast differentiation, attenuated fat accumulation and osteoclast differentiation, and thereby relieved the osteopenic phenotype in the ovariectomized mice. Our study has for the first time established the direct role of OSMR in regulating osteogenic differentiation of marrow stromal progenitor cells through ERK-mediated autophagy signaling. OSMR thus contributes to bone homeostasis through dual regulation of osteoblasts and osteoclasts. It also suggests that OSMR may be a potential target for the treatment of metabolic disorders such as osteoporosis. The online version contains supplementary material available at 10.1186/s13287-022-02958-1.
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DOI：
10.1083/jcb.200610046
发表时间：
2007-02-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
通讯作者：
Franceschi RT
影响因子：
6.2
作者：
Iwaniec, Urszula T.;Yuan, Dawn;Wronski, Thomas J.
通讯作者：
Wronski, Thomas J.
成骨细胞的自噬缺陷会诱导内质网应激并导致显着的骨质流失
影响因子：
13.3
作者：
Li, Huixia;Li, Danhui;Wu, Shufang
通讯作者：
Wu, Shufang
影响因子：
13.3
作者：
Nollet, Marie;Santucci-Darmanin, Sabine;Pierrefite-Carle, Valerie
通讯作者：
Pierrefite-Carle, Valerie
自噬维持骨髓间充质干细胞的功能，预防雌激素缺乏引起的骨质疏松症
影响因子：
12.4
作者：
Qi M;Zhang L;Ma Y;Shuai Y;Li L;Luo K;Liu W;Jin Y
通讯作者：
Jin Y