title: Interplay between CaSR and PTH1R signaling in skeletal development and osteoanabolism.
abstract: Parathyroid hormone (PTH)-related peptide (PTHrP) controls the pace of pre- and post-natal growth plate development by activating the PTH1R in chondrocytes, while PTH maintains mineral and skeletal homeostasis by modulating calciotropic activities in kidneys, gut, and bone. The extracellular calcium-sensing receptor (CaSR) is a member of family C, G protein-coupled receptor, which regulates mineral and skeletal homeostasis by controlling PTH secretion in parathyroid glands and Ca(2+) excretion in kidneys. Recent studies showed the expression of CaSR in chondrocytes, osteoblasts, and osteoclasts and confirmed its non-redundant roles in modulating the recruitment, proliferation, survival, and differentiation of the cells. This review emphasizes the actions of CaSR and PTH1R signaling responses in cartilage and bone and discusses how these two signaling cascades interact to control growth plate development and maintain skeletal metabolism in physiological and pathological conditions. Lastly, novel therapeutic regimens that exploit interrelationship between the CaSR and PTH1R are proposed to produce more robust osteoanabolism.
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Santa Maria
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Alfred
authors.initials: A
authors.lastname: Li
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Jiali
authors.initials: J
authors.lastname: Wang
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Dolores
authors.initials: D
authors.lastname: Shoback
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Tu
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, Veterans Affairs Medical Center, San Francisco, CA, USA. Electronic address: wenhan.chang@ucsf.edu.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Chang
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002356:Cartilage / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000502:physiology; D006132:Growth Plate / Q000502:physiology; D006801:Humans; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000502:physiology; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000502:physiology*; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C095550:CASR protein, human; C473449:PTH1R protein, human; D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D044169:Receptors, Calcium-Sensing; D002118:Calcium
keywords: Calcium-sensing receptor; Growth plate; Osteoporosis; PTH; PTH1R; Rickets