We have cloned the human kidney Ca^<2+>-sensing receptor (CaSR) cDNA and identified a mutation in the gene in a family of familial hypocalciuric hypercalcemia.
From the point of view of calcium metabolism, aging can be assumed in part to result from redistribution of calcium in the body. That is, calcium is transferred from the bone to the arterial walls. It can, therefore, be presumed that this abnormality in calcium metabolism results in arteriosclerosis and osteoporosis.
In this study, we investigated if CaSR is involved in the pathogenesis of arteriosclerosis and osteoporosis.
1) A7r5 is a cell line derived form rat aortic smooth muscle cells. CaSR mRNA is present in the cells. When the cells were stimulated with PDGF (50ng/ml), TGF-beta1 (3ng/ml), IL-1alpha (5ng/ml), IGF-1 (10ng/ml), 17beta-estradiol (10^<-8>M) for 12h, the mRNA levels for CaSR did not changed.
2) UMR-106 is a cell line derived from rat osteosarcoma. We detected the CaSR mRNA in the cells. Therefore, we assumed that the CaSR is involved in osteogenesis. Then, UMR-106 cells were stimulated with 1,25 (OH)_2 vitamin D3 (10^<-6>-10^<-8>M) for 6-24hr, the expression of the CaSR mRNA did not changed. When the cells were cultured in Ca^<2+>-free medium for 36h and then Ca^<2+> was added to 2mM for additional 6 or 12h, the CaSR mRNAs were decreased to the half levels of that of the control. When 17beta-estradiol (10^<-8>M), TGE-beta1 (3ng/ml), PDGF (50ng/ml), IL-1alpha (5ng/ml), IGF-1 (10ng/ml), retinoic acid (10^<-6>M), rat PTH(10^<-8>M) were added for 24h, the expression levels of the mRNA did not altered.
From these studies, although CaSR is expressed in the aortic smooth muscles and osteoblastic cells, contribution of CaSR to the pathogenesis of arteriosclerosis and osteoporosis is, if any, very little.