Taye Nandaraj, Rodriguez Levon, Iatridis James C, Han Woojin M, Hubmacher Dirk
Orthopedic Research Laboratories, Leni & Peter W. May Department of Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
NPJ Regen Med. 2024 Dec 19;9(1):39. doi: 10.1038/s41536-024-00383-x.
Skeletal muscle regeneration and functional recovery after minor injuries requires the activation of muscle-resident myogenic muscle stem cells (i.e. satellite cells) and their subsequent differentiation into myoblasts, myocytes, and ultimately myofibers. We recently identified secreted ADAMTS-like 2 (ADAMTSL2) as a pro-myogenic regulator of muscle development, where it promoted myoblast differentiation. Since myoblast differentiation is a key process in skeletal muscle regeneration, we here examined the role of ADAMTSL2 during muscle regeneration after BaCl injury. Specifically, we found that muscle regeneration was delayed after ablation of ADAMTSL2 in myogenic precursor cells and accelerated following injection of pro-myogenic ADAMTSL2 protein domains. Mechanistically, ADAMTSL2 regulated the number of committed myoblasts, which are the precursors for myocytes and regenerating myofibers. Collectively, our data support a role for myoblast-derived ADAMTSL2 as a positive regulator of muscle regeneration and provide a proof-of-concept for potential therapeutic applications.
轻度损伤后骨骼肌的再生和功能恢复需要激活肌肉驻留的成肌肌肉干细胞（即卫星细胞），并使其随后分化为成肌细胞、肌细胞，最终形成肌纤维。我们最近鉴定出分泌型类ADAMTS样蛋白2（ADAMTSL2）是肌肉发育的促肌生成调节因子，它能促进成肌细胞分化。由于成肌细胞分化是骨骼肌再生的关键过程，我们在此研究了ADAMTSL2在氯化钡损伤后肌肉再生过程中的作用。具体而言，我们发现成肌前体细胞中ADAMTSL2缺失后肌肉再生延迟，而注射促肌生成的ADAMTSL2蛋白结构域后再生加速。从机制上讲，ADAMTSL2调节定向成肌细胞的数量，而成肌细胞是肌细胞和再生肌纤维的前体。总体而言，我们的数据支持成肌细胞衍生的ADAMTSL2作为肌肉再生的正向调节因子的作用，并为潜在的治疗应用提供了概念验证。
