Regulation of osteoclast differentiation
Regulation of osteoclast differentiation
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DOI：
10.1196/annals.1346.013
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发表时间：
2006-01-01
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影响因子：
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通讯作者：
Roodman, G. David
中科院分区：
文献类型：
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作者：
Roodman, G. David
破骨细胞(OCL)来源于单核-巨噬细胞系。最早可识别的OCL前体是粒细胞-巨噬细胞集落形成单位(CFU-GM)，它产生粒细胞、单核细胞和OCL。然后，CFU-GM来源的细胞分化为有丝分裂后的OCL前体细胞，并融合形成多核OCL。多种因素对OCL的形成和活性都有积极和消极的调节作用。这些包括生长因子，如巨噬细胞集落模拟因子，它模拟早期OCL前体的增殖和防止凋亡，以及RANKL，它是OCL形成的主要介质。大多数诱导OCL分化的因素，如PTHrP、IL-11和前列腺素，都是通过诱导未成熟成骨细胞表面RANKL的表达来实现的。骨保护素是一种诱饵受体，可以阻断RANKL的活性。此外，OCL产生调节OCL形成的自分泌-旁分泌因子，如IL-6，OCL在Paget病中产生高水平的IL-6，从而增加OCL的形成。我们筛选了人和小鼠OCL的cDNA文库，以确定调节OCL活性的自分泌-旁分泌因子。我们确定Annexin-II、MIP-1α、ADAM8、嗜酸性粒细胞趋化因子以及OCL抑制因子1和2参与了OCL的形成。最近，我们已经确定了ADAM8的受体，α(9)β(1)整合素，它似乎对正常的OCL活动至关重要。OCL的分化受外源性激素和细胞因子以及自分泌-旁分泌因子的控制，这些自分泌-旁分泌因子对OCL的增殖和分化起积极或消极的调节作用。
The osteoclast (OCL) is derived from the cells in monocyte-macrophage lineage. The earliest identifiable OCL precursor is the granulocyte-macrophage colony-forming unit (CFU-GM), which gives rise to granulocytes, monocytes, and OCL. CFU-GM-derived cells then differentiate to committed OCL precursors, which are post-mitotic cells, and fuse to form multinucleated OCL. A variety of factors both positively and negatively regulate OCL formation and activity. These include growth factors, such as macrophage colony-simulating factor, which simulates the proliferation and prevents apoptosis of early OCL precursors, and RANK ligand (RANKL), which is the primary mediator of OCL formation. Most factors that induce OCL differentiation, such as PTHrP, IL-11, and prostaglandins, do so by inducing expression of RANKL on, the surface of immature osteoblasts. Osteoprotegerin is a decoy receptor that blocks RANKL activity. In addition, OCL produce autocrine-paracrine factors that regulate OCL formation, such as IL-6, which is produced at high levels by OCL in Paget's disease and increases OCL formation. We screened human and murine OCL cDNA libraries to identify autocrine-paracrine factors that regulate OCL activity. We identified annexin-II, MIP-1 alpha, ADAM8, eosinophil chemotactic factor, and OCL inhibitor factors 1 and 2 as factors involved in OCL formation. Most recently, we have identified the receptor for ADAM8, alpha(9)beta(1) integrin, which appears to be critical for normal OCL activity. OCL differentiation is controlled by exogenous hormones and cytokines as well as autocrine-paracrine factors that positively or negatively regulate OCL proliferation and differentiation.