Wnt7b在糖皮质激素诱导的骨质疏松中的机制研究

It has been well established that glucocorticoid induced osteoporosis is highly associated with preosteoblast differentiation and function. This study is based on previous research that Wnt7B can promote bone formation through noncanonical Wnt signaling pathway, as it can stimulate preosteoblast differentiation and increase its activity. However, It is unknown whether Wnt7B can rescue the inhibited osteoblast differentiation and function caused by exogenous glucocorticoid administration. So in this study we use a Wnt7B overexpression transgenic mice to explore whether Wnt7B can rescue the inhibited osteoblast differentiation and funtion through mTORC1 singaling, then elucidate the role of Wnt7B on the mechanism underlying the glucocorticoid induced osteoporosis,which can provide a strong proof to investigate a new drug for curing the glucocorticoid induced osteoporosis.

糖皮质激素诱导的骨质疏松（GIOP）与前体成骨细胞的分化及功能降低密切相关。本课题基于前期研究发现Wnt7B能通过非经典Wnt信号通路促进骨形成，它能促进前体成骨细胞分化并增加其活性从而促进骨形成。然而Wnt7B能否挽救外源性糖皮质激素所抑制的前体成骨细胞分化及活性，还不得而知。因此本课题通过建立Wnt7B过表达转基因小鼠模型，进一步探讨 Wnt7B能否通过激活mTORC1信号通路挽救外源性糖皮质激素所抑制的成骨细胞分化和功能，明确Wnt7B在糖皮质激素诱导的骨质疏松中的机制，为研发治疗糖皮质激素诱导的骨质疏松新药提供实验理论基础。

当前已有充分证据证明糖皮质激素诱导的骨质疏松（GIOP）与成骨前体细胞的分化与功能具有高度相关性，作为非经典Wnt信号通路，Wnt7b可通过刺激成骨前体细胞的分化与增强活性的方式促进骨形成，但Wnt7b能否挽救外源性糖皮质激素对成骨前体细胞分化与细胞功能的抑制作用尚不明确。在本项研究中，通过慢病毒构建Wnt7b过表达细胞系，进而探究Wnt7b对成骨前体细胞分化与功能受抑制后的挽救作用。这可为糖皮质激素诱导的骨质疏松的治疗与新药研究提供可靠而有力的证据。我们发现，过表达Wnt7b可有效挽救地塞米松对成骨前体细胞分化与细胞功能的抑制作用。