title: GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs.
abstract: Free fatty acids display diverse effects as signalling molecules through GPCRs in addition to their involvement in cellular metabolism. GPR120, a G protein-coupled receptor for long-chain unsaturated fatty acids, has been reported to mediate adipogenesis in lipid metabolism. However, whether GPR120 also mediates osteogenesis and regulates BMMSCs remain unclear. In this study, we showed that GPR120 targeted the bi-potential differentiation of BMMSCs in a ligand dose-dependent manner. High concentrations of TUG-891 (a highly selective agonist of GPR120) promoted osteogenesis via the Ras-ERK1/2 cascade, while low concentrations elevated P38 and increased adipogenesis. The fine molecular regulation of GPR120 was implemented by up-regulating different integrin subunits (α1, α2 and β1; α5 and β3). The administration of high doses of TUG-891 rescued oestrogen-deficient bone loss in vivo, further supporting an essential role of GPR120 in bone metabolism. Our findings, for the first time, showed that GPR120-mediated cellular signalling determines the bi-potential differentiation of BMMSCs in a dose-dependent manner. Additionally, the induction of different integrin subunits was involved in the cytoplasmic regulation of a seesaw-like balance between ERK and p38 phosphorylation. These findings provide new hope for developing novel remedies to treat osteoporosis by adjusting the GPR120-mediated differentiation balance of BMMSCs.
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Lanzhou General Hospital of Lanzhou Military Command, Lanzhou Gansu, 730050, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Jie
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Lu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Ya-Qian
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: KMEB, Molecular Endocrinology, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Health Science Center, Shenzhen University, 3688 Nanhai Ave, Shenzhen 518060, People's Republic of China.
authors.forename: Bao-Hua
authors.initials: BH
authors.lastname: Liu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology*; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016023:Integrins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010666:Phenylpropionates / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D018631:ras Proteins / Q000378:metabolism
chemical_list: C585065:3-(4-((4-fluoro-4'-methyl-(1,1'-biphenyl)-2-yl)methoxy)phenyl)propanoic acid; D001713:Biphenyl Compounds; C498007:FFAR4 protein, mouse; D016023:Integrins; D010666:Phenylpropionates; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018631:ras Proteins