Nitric Oxide and Other Novel Regulators of Bone Metabolism

摘要

Over the last thirty years the rapid advances in molecular and cell biology have been mirrored by a radical revision of our view of bone cell biology occasioned by discovery of a host of new factors important in bone physiology. Thus, the discoveries of calcitonin, CGRP, calcitriol, parathyroid hormone, parathyroid hormone related peptide and several cytokines (for example the interleukins and TGF alpha and beta) have transformed our view of bone cell regulation. Most recently however, a further radical discovery has been made largely by the Amgen group. They identified two major factors osteoprotegerin and osteoprotegerin ligand which appear to have a major role in the control of osteoclast function. Osteoprotegerin is a secreted soluble member of the TNF receptor family and its ligand OPGL is a new member of the TNF super family. The Amgen group showed that OPGL is a key regulator of osteoclastogenesis and of lymphocyte development and lymph node organogenesis. Further, in addition to a key role in osteoclastogenesis, OPGL also enhances acute osteoclast activity. OPG produces osteopetrosis while at similar doses OPGL leads to acute and severe bone loss in vivo. Thus these factors are not merely interesting pharmacological curiosities but clearly play a major and unexpected role in the control of osteoclast function. Their discovery is certain to change our views radically and quite likely have practical therapeutic consequences.