Analysis of osteoclast niche regulated by Wnt signals.

我们检测了Wnt信号在破骨细胞生态位形成中的作用，结果如下。(1)分析破骨细胞生态位，明确破骨细胞前体（quiescent osteoclast precursors， QOP）的特征。(2)研究了非典型Wnt信号在破骨细胞发生中的作用。非典型Wnt信号（Wnt5a-Ror2信号）在破骨细胞发生中发挥重要作用。(3) Wnt5a-Ror2信号增强了QOPs中rank的表达。典型的Wnt信号似乎在破骨细胞发生中没有发挥作用。(4)对QOPs进行基因芯片分析，确定QOPs的特异性标记。但我们未能分离出QOPs的特异性标记。然而，我们发现破骨细胞特异性表达Wnt5a。(5) IL-34是造血组织中QOP生成的重要细胞因子。(6)在OPG缺失（OPG /?）小鼠和过表达rankl的转基因小鼠中检测了牙槽骨丢失。功能/ ?小鼠被证明是牙周炎的常用模型。(7)将可溶性Ror2注入胶原诱导的关节炎小鼠体内，可有效抑制骨破坏。

We examined the role of Wnt signaling for the formation of osteoclast niche, and the results as follows. (1) The osteoclast niche was analyzed and characteristics of osteoclast precursors (quiescent osteoclast precursors, QOP) were clarified. (2) The role of noncanonical Wnt signaling in osteoclastogenesis was examined. Noncanonical Wnt signals (Wnt5a-Ror2 signals) were shown to play important roles in osteoclastogenesis. (3) Wnt5a-Ror2 signals enhanced RANKexpression in QOPs. Canonical Wnt signals did not appear to play a role in osteoclastogenesis. (4) GeneChip analysis was performed on QOPs to identify specific markers of QOPs. But we failed to isolate specific markers of QOPs. However, we found that osteoclasts specifically express Wnt5a.(5) IL-34 was identified as an important cytokine for generation of QOP in hematopoietic tissues. (6) Alveolar bone loss was examined in OPG-deficient (OPG?/?) mice and RANKL-overexpressing transgenic mice. OPG?/? mice were shown to be a use l model of periodontitis. (7) Administration of soluble form of Ror2 into collagen-induced arthritis mice effectively suppressed bone destruction.