Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation (IBRI), Foundation for Biomedical Research and Innovation at Kobe (FBRI), Kobe 650-0047, Japan.
National Center of Neurology and Psychiatry, Department of Molecular Therapy, National Institute of Neuroscience, Tokyo 187-8502, Japan.
Int J Mol Sci. 2021 Mar 31;22(7):3627. doi: 10.3390/ijms22073627.
Skeletal muscle regeneration is a well-organized process that requires remodeling of the extracellular matrix (ECM). In this study, we revealed the protective role of periostin, a matricellular protein that binds to several ECM proteins during muscle regeneration. In intact muscle, periostin was localized at the neuromuscular junction, muscle spindle, and myotendinous junction, which are connection sites between muscle fibers and nerves or tendons. During muscle regeneration, periostin exhibited robustly increased expression and localization at the interstitial space. Periostin- mice showed decreased muscle weight due to the loss of muscle fibers during repeated muscle regeneration. Cultured muscle progenitor cells from periostin- mice showed no deficiencies in their proliferation, differentiation, and the expression of Pax7, MyoD, and myogenin, suggesting that the loss of muscle fibers in periostin- mice was not due to the impaired function of muscle stem/progenitor cells. Periostin- mice displayed a decreased number of CD31-positive blood vessels during muscle regeneration, suggesting that the decreased nutritional supply from blood vessels was the cause of muscle fiber loss in periostin- mice. These results highlight the novel role of periostin in maintaining muscle mass during muscle regeneration.
骨骼肌肉再生是一个组织有序的过程,需要细胞外基质(ECM)的重塑。在这项研究中,我们揭示了一种细胞外基质蛋白——骨粘连蛋白在肌肉再生中的保护作用。在完整的肌肉中,骨粘连蛋白定位于神经肌肉接头、肌梭和肌腱肌连接点,这些连接点是肌肉纤维和神经或肌腱之间的连接部位。在肌肉再生过程中,骨粘连蛋白在间质空间中表达和定位明显增加。骨粘连蛋白缺失的小鼠由于在反复肌肉再生过程中失去肌肉纤维而导致肌肉重量下降。骨粘连蛋白缺失的肌肉祖细胞在增殖、分化以及 Pax7、MyoD 和 myogenin 的表达方面没有缺陷,这表明骨粘连蛋白缺失的小鼠中肌肉纤维的丢失不是由于肌肉干细胞/祖细胞功能受损所致。骨粘连蛋白缺失的小鼠在肌肉再生过程中 CD31 阳性血管的数量减少,这表明血管提供的营养供应减少是导致骨粘连蛋白缺失的小鼠肌肉纤维丢失的原因。这些结果突出了骨粘连蛋白在肌肉再生过程中维持肌肉质量的新作用。