BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling.

Abstract

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.

• Authors: Yan-Man Zhou, Yu-Ying Yang, Yi-Xuan Jing, Tian-Jiao Yuan, Li-Hao Sun, Bei Tao, Jian-Min Liu, Hong-Yan Zhao
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 35 Issue 5 Pg. 978-993 (05 2020) ISSN: 1523-4681 [Electronic] United States
• PMID: 31914211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Society for Bone and Mineral Research.

Chemical References

• Gdf2 protein, mouse
• Growth Differentiation Factor 2
• NFATC Transcription Factors
• RANK Ligand
• Tnfsf11 protein, mouse

Topics

• Animals
• Bone Resorption
• Cell Differentiation
• Female
• Growth Differentiation Factor 2 (genetics)
• Mice
• NFATC Transcription Factors
• Osteoblasts
• Osteoclasts
• Osteogenesis
• Ovariectomy
• RANK Ligand
• Wnt Signaling Pathway