title: The calcium-sensing receptor complements parathyroid hormone-induced bone turnover in discrete skeletal compartments in mice.
abstract: Although the calcium-sensing receptor (CaSR) and parathyroid hormone (PTH) may each exert skeletal effects, it is uncertain how CaSR and PTH interact at the level of bone in primary hyperparathyroidism (PHPT). Therefore, we simulated PHPT with 2 wk of continuous PTH infusion in adult mice with deletion of the PTH gene (Pth(-/-) mice) and with deletion of both PTH and CaSR genes (Pth(-/-)-Casr (-/-) mice) and compared skeletal phenotypes. PTH infusion in Pth(-/-) mice increased cortical bone turnover, augmented cortical porosity, and reduced cortical bone volume, femoral bone mineral density (BMD), and bone mineral content (BMC); these effects were markedly attenuated in PTH-infused Pth(-/-)-Casr(-/-) mice. In the absence of CaSR, the PTH-stimulated expression of receptor activator of nuclear factor-κB ligand and tartrate-resistant acid phosphatase and PTH-stimulated osteoclastogenesis was also reduced. In trabecular bone, PTH-induced increases in bone turnover, trabecular bone volume, and trabecular number were lower in Pth(-/-)-Casr(-/-) mice than in Pth(-/-) mice. PTH-stimulated genetic markers of osteoblast activity were also lower. These results are consistent with a role for CaSR in modulating both PTH-induced bone resorption and PTH-induced bone formation in discrete skeletal compartments.
authors.affiliation: Calcium Research Laboratory, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Yingben
authors.initials: Y
authors.lastname: Xue
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jingning
authors.initials: J
authors.lastname: Liu
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Karaplis
authors.forename: Martin R
authors.initials: MR
authors.lastname: Pollak
authors.forename: Edward M
authors.initials: EM
authors.lastname: Brown
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.forename: David
authors.initials: D
authors.lastname: Goltzman
mesh_terms: D015502:Absorptiometry, Photon; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D005786:Gene Expression Regulation; D006961:Hyperparathyroidism / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016062:Porosity; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D014057:Tomography, X-Ray Computed
chemical_list: D007527:Isoenzymes; D016328:NF-kappa B; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D012313:RNA; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase