BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling
BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling
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BMP9 通过骨重塑的双重调节减少卵巢切除小鼠的骨丢失
DOI：
10.1002/jbmr.3957
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发表时间：
2020-01
影响因子：
6.2
通讯作者：
Zhao Hong-Yan
中科院分区：
文献类型：
--
作者：
Zhou Yan-Man;Yang Yu-Ying;Jing Yi-Xuan;Yuan Tian-Jiao;Sun Li-Hao;Tao Bei;Liu Jian-Min;Zhao Hong-Yan
骨重塑是动态的，受破骨细胞主导的骨吸收和成骨细胞主导的骨形成的严格调控。这个过程中的不平衡会导致各种病理状况，如骨质疏松症。骨形态发生蛋白9 （Bone morphogenetic protein 9, BMP9）是一种由肝脏产生和分泌的生物分子，具有多种药理作用，包括抗肝纤维化、抗肿瘤、抗心力衰竭和抗糖尿病活性。然而，BMP9对成骨细胞和破骨细胞功能调控的作用及其潜在的分子机制尚未被研究。在本研究中，BMP9通过上调LGR6和激活Wnt/β‐catenin通路，增加了MC3T3‐E1细胞中成骨基因标记物ALP、Cola1、OCN、RUNX2和OSX的表达和ALP活性。BMP9还通过抑制Akt - NF - κB - NFATc1通路抑制核因子κB受体激活因子（NF - κB）配体（RANKL）诱导的骨髓巨噬细胞（BMMs）破骨细胞分化。更重要的是，在卵巢切除（OVX）小鼠模型中，BMP9通过增加骨形成活性和抑制骨吸收活性来减轻骨丢失和改善体内骨生物力学性能。因此，我们目前的工作强调了BMP9在OVX小鼠中通过促进骨合成代谢活性和抑制破骨细胞分化对骨重塑的双重调节作用。©2020美国骨与矿物研究协会。
Bone remodeling is dynamic and is tightly regulated through bone resorption dominated by osteoclasts and bone formation dominated by osteoblasts. Imbalances in this process can cause various pathological conditions, such as osteoporosis. Bone morphogenetic protein 9 (BMP9), a biomolecule produced and secreted by the liver, has many pharmacological effects, including anti‐liver fibrosis, antitumor, anti‐heart failure, and antidiabetic activities. However, the effects of BMP9 on the regulation of osteoblast and osteoclast functions and the underlying molecular mechanism(s) have not yet been investigated. In this study, BMP9 increased the expression of osteoblastogenic gene markers, such as ALP, Cola1, OCN, RUNX2, and OSX, and ALP activity in MC3T3‐E1 cells by upregulating LGR6 and activating the Wnt/β‐catenin pathway. BMP9 also suppressed receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast differentiation of bone marrow macrophages (BMMs) by inhibiting the Akt‐NF‐κB‐NFATc1 pathway. More importantly, in an ovariectomy (OVX) mouse model, BMP9 attenuated bone loss and improved bone biomechanical properties in vivo by increasing bone‐forming activity and suppressing bone resorption activity. Accordingly, our current work highlights the dual regulatory effects that BMP9 exerts on bone remodeling by promoting bone anabolic activity and inhibiting osteoclast differentiation in OVX mice. © 2020 American Society for Bone and Mineral Research.
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影响因子：
4.6
作者：
Maurer T;Zimmermann G;Maurer S;Stegmaier S;Wagner C;Hänsch GM
通讯作者：
Hänsch GM
DOI：
--
发表时间：
2000
期刊：
NIH consensus statement
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.2
作者：
Kim, Ju-Young;Cheon, Yoon-Hee;Oh, Jaemin
通讯作者：
Oh, Jaemin
影响因子：
6.2
作者：
J. Rubin;Z. Schwartz;B. Boyan;X. Fan;N. Case;Buer Sen;Marcus Drab;Deborah Smith;M. Aleman;K. L. Wong;Hai Yao;H. Jo;T. Gross
通讯作者：
J. Rubin;Z. Schwartz;B. Boyan;X. Fan;N. Case;Buer Sen;Marcus Drab;Deborah Smith;M. Aleman;K. L. Wong;Hai Yao;H. Jo;T. Gross
影响因子：
7.2
作者：
Katagiri, Takenobu;Watabe, Tetsuro
通讯作者：
Watabe, Tetsuro