Journal of Osteoporosis and Physical Activity
Open Access

Abstract

The Urocortin System: A Novel Bone Regulatory Triad, Working In Opposition to RANKL/RANK/OPG

K M Lawrence, T R Jackson and P A Townsend

Bone is in a continual state of flux, with old bone being continually replaced by new. This bone turnover, or remodelling, needs to be highly regulated to prevent disorders associated with aberrant bone mass. This process is controlled principally by two cell types, osteoclasts and osteoblasts, which are responsible for bone resorption and deposition respectively. A crucial, well established regulatory mechanism involved in the control of these cells is the RANKL/RANK/ OPG pathway. With this, an osteoblast derived ligand, RANKL, binds to an osteoclastic receptor RANK, producing increased osteoclastogenesis and resorption. In contrast the Ucn system has only recently been found in bone cells, where an osteoblast and osteoclast derived ligand Ucn1, binds to an osteoclast derived receptor CRF-R2β, resulting in inhibition of osteoclastogenesis and resorption. Both systems possess a representative osteoblast derived binding factor with the potential to terminate the ligand signal. In this review we will briefly describe the discovery of the two systems and then go on to compare and contrast the respective components of these two bone regulatory mechanisms. We will review the pathways employed to produce their bone metabolising effects, and finally, we will speculate upon new areas of research which could be exploited to alleviate conditions associated with abnormal bone mass.