Calcium-Sensing Receptors in Chondrocytes and Osteoblasts Are Required for Callus Maturation and Fracture Healing in Mice.

摘要: Calcium and its putative receptor (CaSR) control skeletal development by pacing chondrocyte differentiation mediating osteoblast (OB) function during endochondral bone formation-an essential process recapitulated fracture repair. Here, we delineated the role of CaSR in transition callus chondrocytes into OB lineage subsequent formation at sites explored targeting CaSRs pharmacologically to enhance In cultured from soft calluses a closed, unfixed site, extracellular [Ca2+ ] allosteric agonist (NPS-R568) promoted terminal resident cells attainment an osteoblastic phenotype. Knockout (KO) Casr gene lengthened chondrogenic phase repair increasing cell proliferation but retarded osteogenic activity hard calluses. Tracing growth plate (GP) that express Rosa26-tdTomato showed reduced OBs (by >80%) spongiosa metaphysis addition, KO specifically mature suppressed mineralizing bony Importantly, experiments using PTH (1-34) healing, co-injection NPS-R568 not only normalized hypercalcemic side effects intermittent treatment mice also produced synergistic osteoanabolic These data indicate functional chondrogenesis osteogenesis potential agonism facilitate © 2019 American Society for Bone Mineral Research.