Interplay between CaSR and PTH1R signaling in skeletal development and osteoanabolism. (January 2016)

• Record Type: Journal Article
• Authors: Santa Maria, Christian; Cheng, Zhiqiang; Li, Alfred; Wang, Jiali; Shoback, Dolores; Tu, Chia-Ling; Chang, Wenhan
• Is Part Of: Seminars in cell & developmental biology. Volume 49(2016)
• Page Start: 11
• Page End: 23
• Publication Date: 2016-01
• Subjects: 1, 25D 1, 25-dihydroxyvitamin D -- Agg aggregan -- ALP alkaline phosphatase -- BRU bone remodeling unit -- CaSR extracellular calcium-sensing receptor -- [Ca2+]e extracellular calcium concentration -- Col(I) type I collagen -- α1(I) alpha 1 subunit of the type I collagen -- Col(II) type II collagen -- α1(II) alpha 1 subunit of the type II collagen -- DMP1 dentin matrix protieon-1 -- HPT hyperparathyroidism -- IGF1 insulin-like growth factor 1 -- Ihh Indian hedgehog -- KO gene knockout -- Gcm2 glial cells missing homolog 2 -- GP growth plate -- GPC growth plate chondrocyte -- iPTH daily injection (or intermittent) PTH treatment -- M-CSF macrophage colony-stimulating factor -- μCT micro-computed tomography -- OB osteoblast -- OCL osteoclast -- OCN osteocalcin -- ON osteonectin -- OPG osteoprotegerin -- OPN osteopontin -- PG proteoglycan -- PTC parathyroid cell -- PTG parathyroid gland -- PTH parathyroid hormone -- PTH1R parathyroid hormone 1 receptor -- PTHrP parathyroid hormone-related protein -- RANK receptor activator of nuclear factor kappa-B -- RANKL RANK ligand -- Floxed-CaSR control mice carrying loxP sequences flanking the exon 7 of the Casr gene -- Exon5CaSR-/- mice with insertion a neomycin gene cassette into the exon 5 of the Casr gene -- CartCaSRΔflox/Δflox mice with constitutive ablation of the exon 7 of the Casr gene targeted specifically to chondrocytes -- Tam-CartCaSRΔflox/Δflox mice with tamoxifen-induced ablation of the exon 7 of the Casr gene targeted specifically to chondrocytes -- OBCaSRΔflox/Δflox mice with constitutive osteoclast-specific ablation of the exon 7 of the Casr gene -- PTH-/- mice with global deletion of Pth gene -- Gcm2-/- mice with global deletion of Gcm2; PTH1R -- PTH -- Calcium-sensing receptor -- Osteoporosis -- Rickets -- Growth plate; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2015.12.004
• Languages: English
• ISSNs: 1084-9521

Abstract

Abstract: Parathyroid hormone (PTH)-related peptide (PTHrP) controls the pace of pre- and post-natal growth plate development by activating the PTH1R in chondrocytes, while PTH maintains mineral and skeletal homeostasis by modulating calciotropic activities in kidneys, gut, and bone. The extracellular calcium-sensing receptor (CaSR) is a member of family C, G protein-coupled receptor, which regulates mineral and skeletal homeostasis by controlling PTH secretion in parathyroid glands and Ca 2+ excretion in kidneys. Recent studies showed the expression of CaSR in chondrocytes, osteoblasts, and osteoclasts and confirmed its non-redundant roles in modulating the recruitment, proliferation, survival, and differentiation of the cells. This review emphasizes the actions of CaSR and PTH1R signaling responses in cartilage and bone and discusses how these two signaling cascades interact to control growth plate development and maintain skeletal metabolism in physiological and pathological conditions. Lastly, novel therapeutic regimens that exploit interrelationship between the CaSR and PTH1R are proposed to produce more robust osteoanabolism.