Roodman G D
Department of Medicine, University of Texas Health Science Center, San Antonio, USA.
Endocr Rev. 1996 Aug;17(4):308-32. doi: 10.1210/edrv-17-4-308.
Much has been learned about the cell biology and molecular biology of the osteoclast in the last 5 yr. The osteoclast appears to be derived from CFU-GM, the committed monocyte-granulocyte precursor cell. This cell then differentiates into more committed precursors for the osteoclast. The role of the marrow microenvironment appears to be critical for murine osteoclast formation, although in human systems it appears to be nonessential but acts to enhance osteoclast formation and resorption. The osteoclast has been shown to be a secretory cell capable of producing both stimulators and inhibitors of osteoclast formation and resorption. The identification of the role of protooncogenes, such as c-fos and pp60c-src, in osteoclast differentiation and bone resorption has provided important insights into the regulation of normal osteoclast activity. Studies such as these should help us to dissect the pathophysiology of abnormal osteoclastic activity, such as seen in hypercalcemia of malignancy, osteopetrosis, and Paget's disease of bone. Future research is needed to further delineate the signaling pathways involved in osteoclastic bone resorption in response to cytokines and hormones, as well as to identify the molecular events required for commitment of multipotent precursors to the osteoclast lineage. Development of osteoclast cell lines may be possible and would greatly enhance our understanding of the biology of the osteoclast. Utilization of current model systems to examine the effects of cytokines and hormones on osteoclast precursors in vitro and in vivo and the ability to obtain large numbers of highly purified osteoclasts for production of osteoclast cDNA libraries should lead to important new discoveries in osteoclast biology.
在过去5年里，我们对破骨细胞的细胞生物学和分子生物学有了很多了解。破骨细胞似乎起源于CFU-GM，即定向单核细胞-粒细胞前体细胞。然后，这种细胞分化为更定向的破骨细胞前体。骨髓微环境的作用似乎对小鼠破骨细胞的形成至关重要，尽管在人类系统中它似乎并非必不可少，但可促进破骨细胞的形成和吸收。破骨细胞已被证明是一种分泌细胞，能够产生破骨细胞形成和吸收的刺激物和抑制剂。原癌基因，如c-fos和pp60c-src，在破骨细胞分化和骨吸收中的作用的确定，为正常破骨细胞活性的调节提供了重要的见解。这类研究应有助于我们剖析异常破骨细胞活性的病理生理学，如在恶性肿瘤高钙血症、骨质石化症和骨佩吉特病中所见。未来的研究需要进一步阐明破骨细胞对细胞因子和激素作出反应时骨吸收所涉及的信号通路，以及确定多能前体定向分化为破骨细胞谱系所需的分子事件。破骨细胞系的开发也许是可行的，这将极大地增进我们对破骨细胞生物学的理解。利用当前的模型系统来研究细胞因子和激素在体外和体内对破骨细胞前体的影响，以及获得大量高度纯化的破骨细胞以构建破骨细胞cDNA文库的能力，应该会在破骨细胞生物学领域带来重要的新发现。
