title: The role of R-spondins and their receptors in bone metabolism.
abstract: R-spondins are a family of four secreted proteins and act as agonists of the canonical Wnt/β-catenin signaling pathway. They are broadly expressed in different phases of skeleton tissues. Recently, three closely related leucine-rich repeat containing G-protein-coupled receptors (Lgr4/5/6) have been identified as the new and exact receptors of R-spondins. On the cell surface, R-spondins binding with Lgr4/5/6 and Znrf3/Rnf43 lead to reduced turnover of Wnts-receptors and potentiate Wnt/β-catenin signaling pathway which is critical for the control of bone development and remodeling. There has been a growing interest in understanding the role and mechanism of R-spondins and their receptors in multiple biological processes, including bone development and metabolism. Recent advances in the R-spondins revealed the potential modulatory effect on osteoblastogenesis and bone formation and provided a new avenue for the investigation of adult bone metabolism. The receptors of Lgr4/5/6 and stabilized β-catenin are essential to the regulatory effect of Rspos on skeleton. The findings on Rspo/Lgr signaling might have clinical potentials for the treatment of bone loss related diseases.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Gui-Xun
authors.initials: GX
authors.lastname: Shi
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Mao
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. Electronic address: zxf272@126.com.
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China. Electronic address: jiangleisheng@126.com.
authors.forename: Lei-Sheng
authors.initials: LS
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D018955:CD36 Antigens; D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins
keywords: Bone metabolism; Lgr4/5/6; R-spondins; Wnt/β-catenin signaling; Znrf3/Rnf43