New concepts in bone remodeling: an expanding role for the osteoblast

Until recently, the prevailing view regarding the function of osteoblasts and osteoclasts was to attribute bone formation to the former and bone resorption to the latter. While the capacity of the osteoclast to degrade bone matrix remains unquestioned, there is now provocative evidence indicating that the osteoblast plays a critical role in regulating osteoclast resorptive activity as well as in contributing directly to matrix dissolution. The first of these points follows from observations indicating that the osteoblast (but not the osteoclast) 1) exhibits receptors and/or responses to resorption-promoting agents (including parathyroid hormone and vitamin D), and 2) releases agents capable of stimulating bone resorption. The second point is derived from studies demonstrating that the osteoblast produces neutral collagenase (an enzyme specialized to degrade type I collagen, the principal organic constituent of bone matrix) and an inhibitor capable of blocking collagenase activity. The synthesis of both of these proteins is, in part, regulated by parathyroid hormone and other resorption-stimulating agents and appears to involve control at the transcriptional, translational, and secretory levels. Thus, in both physiologic bone remodeling and modeling, as well as the altered bone turnover associated with some disease states, it is the osteoblast rather than the osteoclast that may hold the key to understanding the mechanism of tissue form and function.