title: LGR4 acts as a key receptor for R-spondin 2 to promote osteogenesis through Wnt signaling pathway.
abstract: R-spondin proteins are identified as secreted agonists of the canonical Wnt/β-catenin signaling pathway, and leucine-rich repeat-containing G-protein-coupled receptors (LGR) are recognized as R-spondin receptors. The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood. In our in vitro experiments, we found that Rspo2 could promote osteogenesis through activating the Wnt signaling pathway in MC3T3-E1 cells. However, this effect of Rsop2 disappeared in the cells with functional disruption of LGR4. Meanwhile, Rspo2 significantly inhibited osteoclastogenesis and this effect of Rspo2 was dependent on the presence of osteoblasts with normal function of LGR4. In our in vivo experiments, we found that application of exogenous Rspo2 rescued the bone loss and improved the microarchitecture of bone in OVX mice. Rspo2 could be a positive regulator of bone metabolism through activating the canonical Wnt/β-catenin signaling, and LGR4 acted as a key receptor for Rspo2 to promote osteogenesis.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Yu-Ren
authors.initials: YR
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: jiangsd@126.com.
authors.forename: Sheng-Dan
authors.initials: SD
authors.lastname: Jiang
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: jiangleisheng@126.com.
authors.forename: Lei-Sheng
authors.initials: LS
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D020868:Gene Silencing; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D010052:Ovariectomy; D055550:Protein Stability; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D019699:Thrombospondins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism; D000098907:R-Spondins
chemical_list: D060492:Low Density Lipoprotein Receptor-Related Protein-5; D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins; D051176:beta Catenin; C496200:LGR4 protein, mouse; C555483:Lrp5 protein, mouse; C518904:RSPO2 protein, mouse; D000098907:R-Spondins
keywords: LGR4; Osteoblast; Osteoclast; R-spondin 2; Wnt/β-catenin signaling