Role of the endothelial cell in osteoclast control: new perspectives.
The osteoclast is of central importance in the process of bone remodeling. Its function is regulated by hormones and locally produced factors. Endothelial cells occur in close proximity to the osteoclast. Some endothelial cell-derived products, including endothelins, nitric oxide, and reactive oxygen species, have been recently implicated as modulators of osteoclast function. Endothelins inhibit bone resorption and osteoclast margin ruffling (quiescence or Q effect) at concentrations similar to those effective for their primary vasoconstrictive action. Contrary to expectations, however, it has been shown that endothelin action on the osteoclast is not mediated through an elevation of cytosolic Ca2+. Nitric oxide (NO) produces marked cell retraction (retraction or R effect), but its detailed mode of action is unknown. However, it is clear that the effects of this autocoid are not due to enhanced cyclic guanosine monophosphate (cGMP) production, a transduction system commonly used by NO. Finally, the reactive oxygen species H2O2 has been shown recently to enhance osteoclastic activity. Thus, the reported effects of the endothelial cell-derived products on the osteoclast are generally consistent with a regulatory role for endothelial cells in osteoclast control and suggest the existence of unique activation pathways, well worth exploring further. Unravelling the responsible mechanisms may also help understand the pathophysiology of a range of bone and joint diseases. For example, in rheumatoid arthritis, there is increased H2O2 production from activated neutrophils, and bone resorption is a major pathophysiological feature.
Department of Biochemical Medicine, St. George's Hospital Medical School, London, U.K.
M
M
Zaidi
A S
AS
Alam
B E
BE
Bax
V S
VS
Shankar
C M
CM
Bax
J S
JS
Gill
M
M
Pazianas
C L
CL
Huang
T
T
Sahinoglu
B S
BS
Moonga
D016723:Bone Remodeling / Q000502:physiology*; D002116:Calcitonin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D016232:Endothelins / Q000502:physiology; D004727:Endothelium / Q000166:cytology / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D016232:Endothelins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002116:Calcitonin; D000242:Cyclic AMP