title: RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling.
abstract: The four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling. Further, silencing of LGR4 inhibited the activity of ERK signalling and osteogenic differentiation of hASCs. Most importantly, we found that loss of LGR4 abrogated RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signalling inhibition. Collectively, our data show that ERK signalling works downstream of LGR4 and RSPO3 regulates osteoblastic differentiation of hASCs possibly via the LGR4-ERK signalling.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Longwei
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.|National Engineering Lab for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D019699:Thrombospondins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000098907:R-Spondins
chemical_list: D000469:Alkaline Phosphatase; D002070:Butadienes; D050659:Core Binding Factor Alpha 1 Subunit; D005346:Fibroblast Growth Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D009570:Nitriles; D015675:Osteocalcin; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D019699:Thrombospondins; C411562:LGR4 protein, human; C475438:RSPO3 protein, human; D000098907:R-Spondins; C113580:U 0126