Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone

The mass of regenerating tissues, such as bone, is critically dependent on the number of executive cells, which in turn is determined by the rate of r eplication of progenitors and the life-span of mature cells, reflecting the timing of death by apoptosis. Bone mass can be increased by intermittent p arathyroid hormone (PTH) administration, but the mechanism of this phenomen on has remained unknown. We report that daily PTH injections in mice with e ither normal bone mass or osteopenia due to defective osteoblastogenesis in creased bone formation without affecting the generation of new osteoblasts. Instead, PTH increased the life-span of mature osteoblasts by preventing t heir apoptosis - the fate of the majority of these cells under normal condi tions. The antiapoptotic effect of PTH was sufficient to account for the in crease in bone mass, and was confirmed in vitro using rodent and human oste oblasts and osteocytes. This evidence provides proof of the basic principle that the work performed by a cell population can be increased by suppressi on of apoptosis. Moreover, it suggests novel pharmacotherapeutic strategies for osteoporosis and, perhaps, other pathologic conditions in which tissue mass diminution has compromised functional integrity.