Gs/Gi Regulation of Bone Cell Differentiation: Review and Insights from Engineered Receptors

E. C. Hsiao; S. M. Millard; R. A. Nissenson

doi:10.1055/s-0042-116156

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2016; 48(11): 689-699
DOI: 10.1055/s-0042-116156

Review

G_s/G_i Regulation of Bone Cell Differentiation: Review and Insights from Engineered Receptors

Authors

E. C. Hsiao

¹Division of Endocrinology and Metabolism and the Institute for Human Genetics, Department of Medicine, University of California, San Francisco, CA, USA
S. M. Millard

²The University of Queensland-Mater Research Institute, Translational Research Institute, Kent Street, Woolloongabba, QLD, Australia
R. A. Nissenson

³Endocrine Research Unit, VA Medical Center, and Departments of Medicine and Physiology, University of California, San Francisco, CA

⁴Department of Medicine, University of California, San Francisco, CA, USA

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 G_s and G_i pathways increase or decrease intracellular cAMP levels, respectively, by acting on adenylate cyclase, while the G_q pathway 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 G_s and G_i GPCR signaling in osteoblast function. We describe the successful application of a strategy for directly manipulating the G_s and G_i pathways 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.

Key words

osteoblast - stem cells - G-protein coupled receptor - engineered receptor

Full Text

References

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