Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years. Causes of bone defect include tumors, inflammation, and fractures. Bone tissue engineering is a novel treatment of bone defect, and human mesenchymal stem cells (hMSCs) are the ideal seed cells for bone tissue engineering due to their multi-lineage differentiation potential and immunogenicity. The laminin α2 (LAMA2) gene encodes the α2 subunit of laminins. Mutations in this gene have been reported to cause muscular dystrophy, but thus far no studies have elucidated the role of LAMA2 in the fate choices of MSCs. Here, we aimed to investigate the critical role of LAMA2 in the osteogenesis and adipogenesis of mesenchymal stem cells (MSCs). We investigated LAMA2 function in osteogenic and adipogenic differentiation of MSCs in vitro and in vivo through loss- and gain-of-function experiments. In addition, molecular mechanism was clarified by Western blot and siRNA. Our results demonstrated that LAMA2 was a critical regulator for fate commitment of MSCs. Both in vitro and in vivo studies indicate that LAMA2 inhibits osteogenesis and promotes adipogenesis. Mechanistically, we found that LAMA2 regulated osteogenesis and adipogenesis of MSCs by modulating the hedgehog signaling pathway. The present work confirms that LAMA2 is a new molecular target for MSC-based bone regeneration.

中文翻译：

---

LAMA2 通过刺猬信号调节间充质干细胞的命运承诺。

骨缺损是一种常见的临床疾病，近年来受到越来越多的关注。骨缺损的原因包括肿瘤、炎症和骨折。骨组织工程是一种新型的骨缺损治疗方法，人间充质干细胞（hMSCs）具有多向分化潜能和免疫原性，是理想的骨组织工程种子细胞。层粘连蛋白α2（LAMA2）基因编码层粘连蛋白的α2亚基。据报道，该基因的突变会导致肌营养不良，但迄今为止还没有研究阐明 LAMA2 在 MSCs 命运选择中的作用。在这里，我们旨在研究 LAMA2 在间充质干细胞 (MSCs) 的成骨和脂肪形成中的关键作用。我们通过功能丧失和获得实验研究了 LAMA2 在体外和体内 MSCs 成骨和成脂分化中的功能。此外，通过蛋白质印迹和siRNA阐明了分子机制。我们的结果表明，LAMA2 是 MSCs 命运承诺的关键调节因子。体外和体内研究均表明 LAMA2 抑制成骨并促进脂肪生成。机制上，我们发现LAMA2通过调节hedgehog信号通路来调节MSCs的成骨和脂肪生成。目前的工作证实 LAMA2 是基于 MSC 的骨再生的新分子靶点。体外和体内研究均表明 LAMA2 抑制成骨并促进脂肪生成。机制上，我们发现LAMA2通过调节hedgehog信号通路来调节MSCs的成骨和脂肪生成。目前的工作证实 LAMA2 是基于 MSC 的骨再生的新分子靶点。体外和体内研究均表明 LAMA2 抑制成骨并促进脂肪生成。机制上，我们发现LAMA2通过调节hedgehog信号通路来调节MSCs的成骨和脂肪生成。目前的工作证实 LAMA2 是基于 MSC 的骨再生的新分子靶点。