Zaidi M, Alam A S, Bax B E, Shankar V S, Bax C M, Gill J S, Pazianas M, Huang C L, Sahinoglu T, Moonga B S
Department of Biochemical Medicine, St. George's Hospital Medical School, London, U.K.
Bone. 1993 Mar-Apr;14(2):97-102. doi: 10.1016/8756-3282(93)90234-2.
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.
破骨细胞在骨重塑过程中至关重要。其功能受激素和局部产生的因子调节。内皮细胞与破骨细胞紧密相邻。最近，一些内皮细胞衍生产物，包括内皮素、一氧化氮和活性氧，被认为是破骨细胞功能的调节因子。内皮素在与产生主要血管收缩作用相似的浓度下抑制骨吸收和破骨细胞边缘皱襞（静止或Q效应）。然而，与预期相反，已表明内皮素对破骨细胞的作用不是通过胞质Ca2+升高介导的。一氧化氮（NO）可引起明显的细胞回缩（回缩或R效应），但其详细作用方式尚不清楚。然而，很明显这种自分泌物质的作用不是由于环磷酸鸟苷（cGMP）生成增加，cGMP是NO常用的转导系统。最后，最近已表明活性氧H2O2可增强破骨细胞活性。因此，内皮细胞衍生产物对破骨细胞的报道作用通常与内皮细胞在破骨细胞控制中的调节作用一致，并提示存在独特的激活途径，非常值得进一步探索。阐明相关机制也可能有助于理解一系列骨和关节疾病的病理生理学。例如，在类风湿性关节炎中，活化的中性粒细胞产生的H2O2增加，骨吸收是主要的病理生理特征。
