RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting β-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rank^flox/flox: Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.

RANKL 信号传导对破骨细胞生成至关重要。它在成骨细胞分化和骨形成中的作用尚不清楚。在这里，我们证明 RANK 在小鼠和人类成骨分化过程中的早期骨髓间充质干细胞 (BMSCs) 中表达并迅速下降。RANKL 信号通过促进 β-连环蛋白降解和抑制其合成来抑制成骨。相比之下，RANKL 信号对 BMSCs 的脂肪生成没有显着影响。有趣的是，在具有 Prx1 -Cre 小鼠的 BMSCs 中条件性敲除会导致更高的骨量和增加的骨小梁形成，而与破骨细胞无关。此外，排名^flox/flox : Prx1-Cre 小鼠表现出对卵巢切除术（OVX）诱导的骨质流失的抵抗力。因此，我们的研究结果表明，RANKL 信号通过抑制 BMSCs 的成骨分化和促进破骨细胞生成来调节破骨细胞和成骨细胞。