CALCIUM RECEPTORS (CaRs) play an essential role in mineral homeostasis through their regulation of PTH secretion and renal Ca2+ handling. CaRs, however, are expressed in a surprisingly wide variety of tissues including the brain, skin, breast, intestine, bone, and cartilage. The physiologic functions of CaRs in these diverse systems are of considerable potential interest but still remain largely unknown.

The careful morphologic and histomorphometric studies of the growth plate and skeleton in CaR knockout (J/J) mice by Garner et al.(1) suggest unanticipated functions for CaRs in cartilage and bone development. CaR J/J mice have profound hyperparathyroidism and hypercalcemia but do not show the expected hyperparathyroid bone changes. Instead, they exhibit classic features of rickets including growth retardation, expanded growth plates with reduced calcification, widened metaphyses, the “rachitic rosary” rib deformity, and impaired bone mineralization. Manifestations of the latter disturbance include hyperosteoidosis, a prolonged mineralization lag time, and delayed endochondral bone formation. These findings suggest that CaRs play a role, directly or indirectly, in the orderly mineralization of bone and growth plate cartilage. Which bone cells express CaRs? In initial studies, House et al.(2) reported that CaR protein and transcripts were expressed in several cell types from bone marrow including a population that expresses the enzyme alkaline phosphatase, a marker of the osteoblast lineage. Subsequently, other investigators detected CaR RNA by Northern analysis and RT-PCR and CaR protein by immunoblotting and immunocytochemistry in several standard osteoblastic cell lines (3). Studies examining bovine and rat bone sections demonstrated that osteoblasts, osteocytes, and some osteoclasts express CaRs by in situ hybridization and immunocytochemistry (4). High extracellular Ca2+ and other divalent and polyvalent cations stimulated proliferation and chemotaxis in several of the osteoblastic cell lines (3). Interpreting these responses to Ca2+ in the context of bone remodeling, one might envision the following scenario—that extracellular Ca2+-sensing mechanisms in the membranes of osteoblasts enable the cells to home to sites of active bone resorption, where local Ca2+ levels can reach as high as 8–40 mM. There the osteoblasts are stimulated to divide and then participate in the repair of the resorption cavity, thus completing the cycle of bone remodeling.