Abstract
BackgroundBone 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).MethodsWe 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.ResultsOur 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.ConclusionsThe present work confirms that LAMA2 is a new molecular target for MSC-based bone regeneration.
Highlights
Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years
Laminin α2 (LAMA2) is involved in mesenchymal stem cells (MSCs) cell fate determination We studied the expression profile of LAMA2 to determine its involvement in osteogenic differentiation
We investigate the status of LAMA2 in mice bone marrow mesenchymal stem cells
Summary
Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years. The laminin α2 (LAMA2) gene encodes the α2 subunit of laminins Mutations in this gene have been reported to cause muscular dystrophy, but 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). Mesenchymal stem cells (MSCs) are the current focus of researchers as they can self-regenerate, have multidirectional differentiation ability, and are easy to obtain; they are a good candidate for use as seed cells in bone tissue engineering and have promising clinical prospects. Many studies have demonstrated that MSCs can differentiate into osteoblasts, chondrocytes, and adipocytes [3, 4] These findings have significantly promoted research into tissue engineering [5,6,7].
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