Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co‐Factor in PTH Anabolic Actions in Bone. Issue 7 (19th February 2016)

• Record Type: Journal Article
• Authors: Al‐Dujaili, Saja A.; Koh, Amy J.; Dang, Ming; Mi, Xue; Chang, Wenhan; Ma, Peter X.; McCauley, Laurie K.
• Is Part Of: Journal of cellular biochemistry. Volume 117:Issue 7(2016:Jul.)
• Page Start: 1556
• Page End: 1567
• Publication Date: 2016-02-19
• Subjects: PARATHYROID HORMONE -- CALCIUM SENSING RECEPTOR -- CALCIUM -- OSTEOBLASTS; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25447
• Languages: English
• ISSNs: 0730-2312

Abstract

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. Abstract : Anabolic actions of PTH in bone involve increased deposition of mineralizing matrix, with a potential regulatory feedback role of calcium homeostasis in this process. This investigation studied the role of calcium availability and the calcium sensing receptor (CaSR) in the anabolic actions of PTH. The 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.