Calcium Sensing Receptor Function Supports Osteoblast Survival and Acts as a Co-Factor in PTH Anabolic Actions in Bone
Authors: Peter X Ma
Saja A Al-Dujaili
Laurie K McCauley
Ming Dang
Xue Mi
Amy J Koh
Wenhan Chang
Journal: Journal of Cellular Biochemistry (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CALCIUM; CALCIUM SENSING RECEPTOR; OSTEOBLASTS; PARATHYROID HORMONE.
Affiliations: Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan., Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan., Endocrine Research Unit, University of California, San Francisco, California., 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., Department of Pathology, University of Michigan, Ann Arbor, Michigan.

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. 

Retracted: No

PubPeer comments:
 The authors used in this paper a u201cnewu201d multi-attribute decision making method called MABAC for agroforestry biomass cogeneration projects. The steps of MABAC method are illustrated in Section 4.3. However, it turns out that the u201cnewu201d (claimed by the authors) method is nothing but the weighted average. Specifically, the values used for ranking are calculated by eq.(20) in Step 4. Note that, according to eq.(18), $$S_i = sum_{j=1}^{n}q_{ij} = (v_{i1} -g_1) +cdots + (v_{in}-g_n) = (v_{i1}+cdots +v_{in}) -(g_1+cdots +g_n)$$ According to eq.(15) and eq.(16), with given matrix $V=(v_{ij})$, the value of $g_1+cdots +g_n$ is **a fixed constant**. As a consequence, comparing the values of $$(v_{i1}+cdots +v_{in}) -(g_1+cdots +g_n)$$ is **equivalent to** comparing the values of $$v_{i1}+cdots +v_{in}$$ Moreover, according to eq.(15) in Step 1, it holds that $v_{ij} = w_j(n_{ij} + 1) = w_jn_{ij}+w_j$ and consequently, comparing the values of $$v_{i1}+cdots +v_{in}$$ is **equivalent to** comparing the values of $$(w_1n_{i1}+cdots +w_nn_{in}) +(w_1+cdots +w_n) = (w_1n_{i1}+cdots +w_nn_{in}) +1$$ and also **equivalent to** comparing the values of $$w_1n_{i1}+cdots +w_nn_{in}$$ In other words, **there is no new method**. However, the authors claimed in the beginning of Section 4.3 that the MABAC method u201c**has the superiority of easy implementation, excellent consistency and the ability to observe the distribution of alternatives**u201d Could the authors address this issue? ![file] ![file] ![file] ![file] ![file] ,