A DISTINCT CATION-SENSING MECHANISM IN MC3T3-E1 OSTEOBLASTS FUNCTIONALLY RELATED TO THE CALCIUM RECEPTOR

The presence of a cation-sensing mechanism in osteoblasts is suggested by the ability of specific cations to stimulate osteoblastic prolifer ation in culture and to induce de novo bone formation in some experime ntal models. Our study examines whether extracellular cations stimulat e osteoblasts through the recently identified G protein-coupled calciu m receptor (CaR). We found that CaR agonists, calcium (Ca2+), gadolini um (Gd3+), aluminum (Al3+), and neomycin, stimulated DNA synthesis in murine-derived MC3T3-E1 preosteoblasts, whereas magnesium (Mg2+), nick el (Ni2+), cadmium (Cd2+), and zinc (Zn2+) had no effect. With the exc eption of Mg2+, the cation specificities and apparent affinities were similar to that reported for CaR. CaR agonists also stimulated DNA syn thesis in C3HT10(1/2), fibroblasts, but not in mesangial PVG, CHO, hep atic HTC, COS-7 cells, or malignant transformed ROS17/12.8 and UMR-106 osteoblasts. In addition, similar to other growth factors, CaR agonis ts activated transcription of a serum response element luciferase repo rter construct (SRE-Luc) stably transfected into MC3T3-E1 osteoblasts, but had no effect on SRE-Luc transfected into CHO and COS-7 cells. We were unable to detect CaR expression by Northern analysis using a mou se CaR-specific probe or to amplify CaR mRNA by reverse transcribed po lymerase chain reaction in MC3T3-E1 osteoblasts. These findings sugges t that an extracellular cation-sensing mechanism is present in murine- derived osteoblasts that is functionally similar to but molecularly di stinct from CaR.