title: Gs/Gi Regulation of Bone Cell Differentiation: Review and Insights from Engineered Receptors.
abstract: G-protein coupled receptors (GPCRs) and their ligands are critical for normal osteoblast formation and function. GPCRs mediate a wide variety of biological processes and are activated by multiple types of extracellular signals, ranging from photons to small molecules to peptides. GPCRs signal through a select number of canonical pathways: the Gsand Gipathways increase or decrease intracellular cAMP levels, respectively, by acting on adenylate cyclase, while the Gqpathway increases intracellular calcium by activating phospholipase C. In addition, non-canonical GPCR pathways such as β-arrestin activation are important for osteoblast function. Since many cells express multiple GPCRs, and each individual GPCR may activate multiple signaling pathways, the resulting combinatorial signal provides a mechanism for regulating complex biological processes and effector functions. However, the wide variety of GPCRs, the possibility of multiple receptors acting with signaling redundancy, and the possibility of an individual GPCR activating multiple signaling pathways, also pose challenges for elucidating the role of a particular GPCR. Here, we briefly review the roles of Gsand GiGPCR signaling in osteoblast function. We describe the successful application of a strategy for directly manipulating the Gsand Gipathways using engineered receptors. These powerful tools will allow further elucidation of the roles of GPCR signaling in specific lineages of osteoblastic cells, as well as in non-osteoblast cells, all of which remain critical areas of active research.
authors.affiliation: Division of Endocrinology and Metabolism and the Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Hsiao
authors.affiliation: The University of Queensland-Mater Research Institute, Translational Research Institute, Kent Street, Woolloongabba, QLD, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Millard
authors.affiliation: Endocrine Research Unit, VA Medical Center, and Departments of Medicine and Physiology, University of California, San Francisco, CA.
authors.forename: R A
authors.initials: RA
authors.lastname: Nissenson
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002454:Cell Differentiation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs