The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation.

Strontium ranelate has several beneficial effects on bone and reduces the risk of vertebral and hip fractures in women with postmenopausal osteoporosis. We investigated whether Sr(2+) acts via a cell surface calcium-sensing receptor (CaR) in HEK293 cells stably transfected with the bovine CaR (HEK-CaR) and rat primary osteoblasts (POBs) expressing the CaR endogenously. Elevating Ca(o)(2+) or Sr(2+) concentration-dependently activated the CaR in HEK-CaR but not in non-transfected cells, but the potency of Sr(2+) varied depending on the biological response tested.

Role of the cytoskeleton in extracellular calcium-regulated PTH release.

The calcium-sensing receptor (CaR) mediates the effects of extracellular calcium ([Ca(2+)](o)) on PTH release, such that increasing levels of [Ca(2+)](o) inhibit PTH secretion through poorly defined mechanisms. In the present studies, immunocytochemical analysis demonstrated that F-actin, PTH, CaR, and caveolin-1 are colocalized at the apical secretory pole of PT cells, and subcellular fractionation of PT cells showed these proteins to be present within the secretory granule fraction. High [Ca(2+)](o) caused F-actin, PTH, and caveolin-1 to move to the apical pole of the cells.

The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis.

Intracellular transduction pathways that are dependent on activation of the CaR by Ca(o)2+ have been studied extensively in parathyroid and other cell types, and include cytosolic calcium, phospholipases C, A2, and D, protein kinase C isoforms and the cAMP/protein kinase A system. In this study, using bone marrow cells isolated from CaR-/- mice as well as DN-CaR-transfected RAW 264.7 cells, we provide evidence that expression of the CaR plays an important role in osteoclast differentiation.

Abnormal parathyroid cell proliferation precedes biochemical abnormalities in a mouse model of primary hyperparathyroidism.

The properties of neoplastic proliferation and hormonal dysregulation are tightly linked in primary hyperparathyroidism (HPT). However, whether abnormal parathyroid proliferation is the cause or result of a shift in calcium-sensitive parathyroid hormonal regulation has been controversial. We addressed this issue by analyzing the temporal sequence of these fundamental abnormalities in a mouse model of primary HPT.

Calcium-sensing receptor activation stimulates parathyroid hormone-related protein secretion in prostate cancer cells: role of epidermal growth factor receptor transactivation.

We have previously reported that high extracellular Ca2+ stimulates parathyroid hormone-related protein (PTHrP) release from human prostate and breast cancer cell lines as well as from H-500 rat Leydig cancer cells, an action mediated by the calcium-sensing receptor (CaR). Activating the CaR leads to phosphorylation of mitogen-activated protein kinases (MAPKs) that participate in PTHrP synthesis and secretion. Because the CaR is a G protein-coupled receptor (GPCR), it is likely to transactivate the epidermal growth factor receptor (EGFR) or the platelet-derived growth factor receptor (PDGFR).