Skeletal phenotype of mice with a null mutation in Cav 1.3 L-type calcium channel

This study aimed to understand the role of Cav1.3, one of the four L-type voltage sensitive calcium channels (VSCC) alpha(1) subunits, in the skeletal response to mechanical loading and intermittent PTH treatment. The Cav1.3 mRNA is expressed in osteoblasts. The Cav1.3 mRNA level in male wild type mice is higher than those in female. Loss of Cav1.3 resulted in a smaller skeleton in male mice as indicated by significantly lower body weight, less bone mineral content and smaller cross-sectional area of femoral midshaft. However, the osteogenic response to mechanical loading of the ulna was normal in Cav1.3(-/-) compared to the normal control mice. Male mice Cav1.3(-/-) were then treated daily with PTH at a dose of 40 microg/kg. A 6-week course of intermittent PTH treatment enhanced bone mineral content and mechanical strength equally in wild type control and Cav1.3 null mice. We also found that Cav1.2 subunit significantly increases in the absence of Cav1.3 gene. In conclusion, Cav1.3 is involved in bone metabolism, especially in male mice. Cav1.3 does not mediate osteoblast response to mechanical loading and PTH. Our data suggest that Cav1.1 and Cav1.2 subunits may substitute for Cav1.3 to maintain bone response to mechanical loading.