Relaxin stimulates osteoclast differentiation and activation
Relaxin stimulates osteoclast differentiation and activation
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DOI：
10.1016/j.bone.2009.10.007
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发表时间：
2010-02-01
期刊：
影响因子：
4.1
通讯作者：
Foresta, Carlo
中科院分区：
文献类型：
--
作者：
Ferlin, Alberto;Pepe, Anastasia;Foresta, Carlo
松弛素是一种多效性激素，在生殖和非生殖组织中均有作用，并在肿瘤生物学中发挥作用。它能促进不同肿瘤的生长、分化和侵袭性，尤其是骨转移的肿瘤，骨转移患者血清松弛素浓度升高。在溶骨转移中，骨的破坏是由破骨细胞介导的，破骨细胞是源自造血祖细胞的多核细胞。我们发现人造血前体细胞和成熟破骨细胞表达松弛素受体RXFP1。然后，我们研究了松弛素对人造血祖细胞体外破骨过程中破骨细胞分化、活化和基因表达的影响。单独使用松弛素能够诱导人破骨细胞发生的多步分化过程，其时间与经典的破骨细胞发生刺激剂RANKL、M-CSF和PTH相似。采用定量RT-PCR技术研究了破骨细胞形成过程中多个破骨细胞基因的表达谱。分析结果表明，松弛素诱导的基因与破骨细胞的分化、存活和活化有关。松弛素诱导的破骨细胞完全分化，酒石酸盐抗性酸性磷酸酶和玻璃体连接蛋白受体阳性，表达典型的f -肌动蛋白环，能够吸收骨。此外，松弛素诱导其特异性受体RXFP1在破骨细胞中的表达。本研究首次证明松弛素是造血前体破骨细胞形成的有效刺激物，并调节成熟破骨细胞的活性，为该激素在骨生理、疾病和转移中的作用开辟了新的视角。(C) 2009爱思唯尔公司版权所有。
Relaxin is a pleiotropic hormone with actions in reproductive and non-reproductive tissues, and has a role in tumor biology. It can promote growth, differentiation and invasiveness of different tumors, especially those that give bone metastases, and relaxin serum concentrations are increased in patients with bone metastasis. In osteolytic metastasis the destruction of bone is mediated by osteoclasts that are multinucleated cells derived from hematopoietic progenitors. We found that human hematopoietic precursors and mature osteoclasts express the relaxin receptor RXFP1. Then, we investigated the effects of relaxin on the differentiation, activation and gene expression of osteoclasts during in vitro osteoclastogenesis from human hematopoietic progenitor cells. Relaxin alone was able to induce the multistep differentiation process of human osteoclastogenesis with timing similar to that obtained with the classical stimulators of osteoclastogenesis RANKL, M-CSF and PTH. The expression profile of several osteoclast genes was studied with quantitative RT-PCR during the entire process of osteoclastogenesis. This analysis showed that relaxin induced genes that are implicated in the differentiation, survival and activation of osteoclasts. Relaxin-induced osteoclasts were fully differentiated, positive for tartrate resistant acid phosphatase and vitronectin receptor, expressing a typical F-actin ring and able to resorb the bone. Furthermore, relaxin induced the expression of its specific receptor RXFP1 in osteoclasts. This study demonstrates for the first time that relaxin is a potent stimulator of osteoclastogenesis from hematopoietic precursors and regulates the activity of mature osteoclasts, opening new perspectives on the role of this hormone in bone physiology, diseases and metastasis. (C) 2009 Elsevier Inc. All rights reserved.