Osteoclast-Specific Dicer Gene Deficiency Suppresses Osteoclastic Bone Resorption
Osteoclast-Specific Dicer Gene Deficiency Suppresses Osteoclastic Bone Resorption
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DOI：
10.1002/jcb.22228
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发表时间：
2010-04-01
影响因子：
4
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
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作者：
Mizoguchi, Fumitaka;Izu, Yayoi;Noda, Masaki
破骨细胞是骨的独特细胞，不仅参与骨重建，而且参与病理性骨丢失，如骨质疏松症和类风湿性关节炎。破骨细胞的调节是基于许多分子，但这些分子的全部细节尚未被理解。微RNA是由Dicer切割产生的，Dicer切割是一种新兴的细胞和组织功能调节系统。在这里，我们研究了破骨细胞中Dicer缺乏对体内骨代谢活性和骨量的影响。我们通过将Dicer flox小鼠与组织蛋白酶K-Cre敲入小鼠杂交来特异性敲除破骨细胞中的Dicer。破骨细胞中Dicer缺乏减少体内破骨细胞数量（N.Oc/BS）和破骨细胞表面（Oc.S/BS）。然而，破骨细胞中Dicer缺乏抑制了培养中TRAP阳性多核细胞的发育水平，也降低了NFATc 1和TRAP基因的表达。MicroRNA分析表明，RANKL处理抑制了Dicer缺陷细胞中miR-155的表达。破骨细胞中Dicer缺乏抑制体内成骨细胞活性，包括矿物质沉积率（MAR）和骨形成率（BFR），并且还抑制体内编码I型胶原、骨钙素、Runx 2和Efnb 2的基因的表达。破骨细胞中Dicer缺乏增加了骨量水平，表明Dicer缺乏诱导的成骨细胞抑制优于Dicer缺乏诱导的成骨细胞抑制。另一方面，通过使用2.3kb I型胶原蛋白-Cre在成骨细胞中条件性Dicer缺失不影响骨量。这些结果表明，破骨细胞中的Dicer控制体内骨吸收活性。J.细胞。109：866-875，2010. (C)2009 Wiley-Liss，Inc.
Osteoclasts are unique cells that resort) bone, and are involved in not only bone remodeling but also pathological bone loss such as osteoporosis and rheumatoid arthritis. The regulation of osteoclasts is based on a number of molecules but full details of these molecules have not yet been understood. MicroRNAs are produced by Dicer cleavage an emerging regulatory system for cell and tissue function. Here, we examine the effects of Dicer deficiency in osteoclasts on osteoclastic activity and bone mass in vivo. We specifically knocked out Dicer in osteoclasts by crossing Dicer flox mice with cathepsin K-Cre knock-in mice. Dicer deficiency in osteoclasts decreased the number of osteoclasts (N.Oc/BS) and osteoclast surface (Oc.S/BS) in vivo. Intrinsically, Dicer deficiency in osteoclasts suppressed the levels of TRAP positive multinucleated cell development in culture and also reduced NFATc1 and TRAP gene expression. MicroRNA analysis indicated that expression of miR-155 was suppressed by RANKL treatment in Dicer deficient cells. Dicer deficiency in osteoclasts suppressed osteoblastic activity in vivo including mineral apposition rate (MAR) and bone formation rate (BFR) and also suppressed expression of genes encoding type I collagen, osteocalcin, Runx2, and Efnb2 in vivo. Dicer deficiency in osteoclasts increased the levels of bone mass indicating that the Dicer deficiency-induced osteoclastic suppression was dominant over Dicer deficiency-induced osteoblastic suppression. On the other hand, conditional Dicer deletion in osteoblasts by using 2.3 kb type I collagen-Cre did not affect bone mass. These results indicate that Dicer in osteoclasts controls activity of bone resorption in vivo. J. Cell. Biochem. 109: 866-875, 2010. (C) 2009 Wiley-Liss, Inc.