title: Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co-Factor in PTH Anabolic Actions in Bone.
abstract: Anabolic actions of PTH in bone involve increased deposition of mineralizing matrix. Regulatory feedback of the process may be important to maintain calcium homeostasis and, in turn, calcium may inform the process. This investigation clarified the role of calcium availability and the calcium sensing receptor (CaSR) in the anabolic actions of PTH. CaSR function promoted osteoblastic cell numbers, with lower cell numbers in post-confluent cultures of primary calvarial cells from Col1-CaSR knock-out (KO) mice, and for calvarial cells from wild-type (WT) mice treated with a calcilytic. Increased apoptosis of calvarial cells with calcilytic treatment suggested CaSR is critical for protection against stage-dependent cell death. Whole and cortical, but not trabecular, bone parameters were significantly lower in Col1-CaSR KO mice versus WT littermates. Intact Col1-CaSR KO mice had lower serum P1NP levels relative to WT. PTH treatment displayed anabolic actions in WT and, to a lesser degree, KO mice, and rescued the lower P1NP levels in KO mice. Furthermore, PTH effects on whole tibiae were inhibited by osteoblast-specific CaSR ablation. Vertebral body implants (vossicles) from untreated Col1-CaSR KO and WT mice had similar bone volumes after 4 weeks of implantation in athymic mice. These findings suggest that trabecular bone formation can occur independently of the CaSR, and that the CaSR plays a collaborative role in the PTH anabolic effects on bone. J. Cell. Biochem. 117: 1556-1567, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Saja A
authors.initials: SA
authors.lastname: Al-Dujaili
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Koh
authors.affiliation: Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Ming
authors.initials: M
authors.lastname: Dang
authors.affiliation: Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan.
authors.forename: Xue
authors.initials: X
authors.lastname: Mi
authors.affiliation: Endocrine Research Unit, University of California, San Francisco, California.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Chang
authors.affiliation: Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan.|Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan.|Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan.|Department of Pathology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
mesh_terms: D000818:Animals; D002118:Calcium; D002470:Cell Survival; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D010010:Osteoclasts; D010012:Osteogenesis / Q000502:physiology*; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012886:Skull / Q000378:metabolism*
chemical_list: C577923:CASR protein, mouse; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011347:Procollagen; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; C047202:procollagen Type I N-terminal peptide; D002118:Calcium
keywords: CALCIUM; CALCIUM SENSING RECEPTOR; OSTEOBLASTS; PARATHYROID HORMONE