Myosin 1a Regulates Osteoblast Differentiation Independent of Intestinal Calcium Transport.

Myosin 1A (Myo1a) is a mechanoenzyme previously thought to be located exclusively in the intestinal epithelium. It is the principle calmodulin-binding protein of the brush border. Based on earlier studies in chickens, we hypothesized that Myo1a facilitates calcium transport across the brush border membrane of the intestinal epithelium, perhaps in association with the calcium channel Trpv6. Working with C2Bbe1 cells, a human intestinal epithelial cell line, we observed that overexpression of Myo1a increased, whereas the antisense construct blocked calcium transport. To further test this hypothesis, we examined mice in which either or both and had been deleted. Although the -null mice had decreased intestinal calcium transport, the -null mouse did not, disproving our original hypothesis, at least in mice. Expecting that a reduction in intestinal calcium transport would result in decreased bone, we examined the skeletons of these mice. To our surprise, we found no decrease in bone in the -null mouse, but a substantial decrease in the -null mouse. Double deletions were comparable to the null. Moreover, Myo1a but not Trpv6 was expressed in osteoblasts. , the bone marrow stromal cells from the -null mice showed normal numbers of colony-forming units but marked decrements in the formation of alkaline phosphatase-positive colonies and mineralized nodules. We conclude that Myo1a regulates osteoblast differentiation independent of its role, if any, in intestinal calcium transport, whereas Trpv6 functions primarily to promote intestinal calcium transport with little influence in osteoblast function.