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

Calcium and its putative receptor (CaSR) control skeletal development by pacing chondrocyte differentiation and mediating osteoblast (OB) function during endochondral bone formation-an essential process recapitulated during fracture repair. Here, we delineated the role of the CaSR in mediating transition of callus chondrocytes into the OB lineage and subsequent bone formation at fracture sites and explored targeting CaSRs pharmacologically to enhance fracture repair. In chondrocytes cultured from soft calluses at a closed, unfixed fracture site, extracellular [Ca ] and the allosteric CaSR agonist (NPS-R568) promoted terminal differentiation of resident cells and the attainment of an osteoblastic phenotype.

Sex and age modify biochemical and skeletal manifestations of chronic hyperparathyroidism by altering target organ responses to Ca2+ and parathyroid hormone in mice.

We studied mice with or without heterozygous deletion of the Casr in the parathyroid gland (PTG) [(PTG) CaSR(+/-)] to delineate effects of age and sex on manifestations of hyperparathyroidism (HPT). In control mice, aging induced a left-shift in the Ca(2+) /parathyroid hormone (PTH) set point accompanied by increased PTG CaSR expression along with lowered serum Ca(2+) and mildly increased PTH levels, suggesting adaptive responses of PTGs to aging-induced changes in mineral homeostasis. The aging effects on Ca(2+) /PTH set point and CaSR expression were significantly blunted in (PTG) CaSR(+/-) mice, who showed instead progressively elevated PTH levels with age, especially in 12-month-old females.