Receptor tyrosine kinase-like orphan receptor 2 (Ror2) plays a key role in bone formation, but its signaling pathway is not completely understood. Signal transducer and activator of transcription 3 (Stat3) takes part in maintaining bone homeostasis. The aim of this study is to reveal the role and mechanism of Ror2 in the osteogenic differentiation from mouse bone marrow mesenchymal stem cells (mBMSCs) and to explore the effect of Stat3 on Ror2-mediated osteogenesis. Ror2 CKO mice were generated via the Cre-loxp recombination system using Prrx1-Cre transgenic mice. Quantitative real-time PCR and western blot were performed to assess the expression of Stat3 and osteogenic markers in Ror2-knockdown mBMSCs (mBMSC-sh-Ror2). After being incubated in osteogenic induction medium for 3 weeks, Alizarin Red staining and western blot were used to examine the calcium deposit and osteogenic markers in Stat3 overexpression in mBMSC-sh-Ror2. Loss of Ror2 in mesenchymal or osteoblast progenitor cells led to a dwarfism phenotype in vivo. The mRNA expression of osteogenic markers (osteocalcin, osteopontin (OPN), and collagen I) in the ulna proximal epiphysis of Ror2 CKO mice was significantly decreased (P < 0.05). The mRNA and protein expression of Stat3 and osteogenic markers (Runx2, osterix, and OPN) decreased in mBMSC-sh-Ror2 cells (P < 0.05). The overexpression of Stat3 in mBMSC-sh-Ror2 cells rescued the calcium deposit and expression of Runx2, osterix, and OPN to a level comparable to normal mBMSCs. Ror2 was essential for skeleton development by regulating mBMSCs’ osteogenesis and osteoblast differentiation. Loss of Ror2 may impair the osteogenesis of mBMSCs by inhibiting Stat3.

中文翻译：

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受体酪氨酸激酶样孤儿受体2的丢失通过抑制信号转导子和转录激活子3损害了mBMSC的成骨作用。

受体酪氨酸激酶样孤儿受体2（Ror2）在骨形成中起关键作用，但其信号传导途径尚不完全清楚。信号转导和转录激活因子3（Stat3）参与维持骨稳态。这项研究的目的是揭示Ror2在小鼠骨髓间充质干细胞（mBMSCs）成骨分化中的作用和机制，并探讨Stat3对Ror2介导的成骨作用的影响。使用Prrx1-Cre转基因小鼠通过Cre-loxp重组系统生成Ror2 CKO小鼠。进行实时定量PCR和Western印迹以评估Stat3和成骨标记在Ror2-敲除mBMSC（mBMSC-sh-Ror2）中的表达。在成骨诱导培养基中孵育3周后，茜素红染色和蛋白质印迹用于检查mBMSC-sh-Ror2中Stat3过表达中的钙沉积和成骨标记。间充质或成骨祖细胞中Ror2的丢失导致体内侏儒症表型。Ror2 CKO小鼠尺骨近端骨epi中成骨标记物（骨钙蛋白，骨桥蛋白（OPN）和胶原蛋白I）的mRNA表达显着降低（P <0.05）。在mBMSC-sh-Ror2细胞中，Stat3和成骨标记物（Runx2，osterix和OPN）的mRNA和蛋白表达下降（P <0.05）。Stat3在mBMSC-sh-Ror2细胞中的过表达将钙沉积和Runx2，osterix和OPN的表达恢复到与正常mBMSC相当的水平。Ror2通过调节mBMSC的成骨作用和成骨细胞分化对于骨骼发育至关重要。