G Protein and its signaling pathway in bone development and disease.

G protein signaling is comprised of G protein coupled receptors (GPCRs) that detect ligands or sense cations, heterotrimeric G proteins, and downstream effectors and regulators. G protein signaling plays important roles in bone development, remodeling, and disease. In human cases, mutations of certain GPCRs and G proteins impair bone development and metabolism, resulting in bone diseases. This review focuses on the functions of G proteins and GPCRs in osteoblasts and osteoclasts, their signaling pathways, and their gene mutations in mouse models and human diseases. We have discussed the roles of all four types of G proteins (i.e. Gs, Gq/11, Gi/o, and G12/13) and assessed the roles of the GPCRs, such as type 1 Parathyroid hormone receptor (PTH1R), calcitonin receptor, cation sensing receptor (CaSR), relaxin family peptides, cannabinoid receptor, frizzleds, and proton sensing receptor in normal bone formation and remodeling. The roles of regulators of G protein signaling (RGS) and GTPase-activating proteins (GAP) in G-protein signaling pathways are also reviewed. Lastly, we give perspective for the research of G protein signaling in bone development and disease.