Al-Dujaili Saja A, Koh Amy J, Dang Ming, Mi Xue, Chang Wenhan, Ma Peter X, McCauley Laurie K
Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, Michigan.
Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, Michigan.
J Cell Biochem. 2016 Jul;117(7):1556-67. doi: 10.1002/jcb.25447. Epub 2016 Feb 19.
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.
甲状旁腺激素(PTH)在骨骼中的合成代谢作用包括矿化基质沉积增加。该过程的调节反馈对于维持钙稳态可能很重要,反过来,钙也可能影响这一过程。本研究阐明了钙的可利用性和钙敏感受体(CaSR)在PTH合成代谢作用中的作用。CaSR功能促进成骨细胞数量增加,来自Col1-CaSR基因敲除(KO)小鼠的原代颅骨细胞汇合后培养物中的细胞数量较少,而用钙解素处理的野生型(WT)小鼠的颅骨细胞也是如此。用钙解素处理后颅骨细胞凋亡增加,表明CaSR对于防止阶段依赖性细胞死亡至关重要。与WT同窝小鼠相比,Col1-CaSR KO小鼠的整体骨和皮质骨(而非小梁骨)参数显著更低。完整的Col1-CaSR KO小鼠的血清I型前胶原氨基端前肽(P1NP)水平相对于WT更低。PTH治疗在WT小鼠中显示出合成代谢作用,在KO小鼠中作用程度较小,并挽救了KO小鼠中较低的P1NP水平。此外,成骨细胞特异性CaSR缺失抑制了PTH对整个胫骨的作用。未经处理的Col1-CaSR KO和WT小鼠的椎体植入物(小骨块)在无胸腺小鼠中植入4周后具有相似的骨体积。这些发现表明小梁骨形成可以独立于CaSR发生,并且CaSR在PTH对骨骼的合成代谢作用中起协同作用。《细胞生物化学杂志》117: 1556 - 1567, 2016年。© 2015威利期刊公司