Recombinant ADAMTS‑1 promotes muscle regeneration accompanied by downregulation of Notch signaling

Skeletal muscle satellite cells (MuSCs) play a central role in muscle regeneration; however, their capacity declines with age, contributing to sarcopenia. A disintegrin and metalloproteinase with thrombospondin motifs‑1 (ADAMTS‑1) regulates MuSC activation and differentiation. The present study aimed to investigate the potential of recombinant ADAMTS‑1 (rADAMTS‑1) as a therapeutic strategy to enhance MuSC proliferation and improve regeneration. After barium chloride injection, mice received daily intraperitoneal injections of rADAMTS‑1 at 5 or 10 mg/kg for 1, 3, 7, or 14 days to monitor recovery. Primary skeletal muscle and C2C12 cells were also treated with rADAMTS‑1 to evaluate its effects on gene and protein expression during proliferation and differentiation <i>in vitro</i>. The number of MuSCs and the expression of myogenic markers increased in all injured groups by day 3 post‑injury <i>in vivo</i>. These levels were particularly elevated in the high‑dose rADAMTS‑1 group and remained sustained until day 14. Grip strength recovered to normal levels by day 7 in the high‑dose rADAMTS‑1 group, suggesting improved functional recovery compared with the untreated controls. In vitro, rADAMTS‑1 treatment induced a dose‑dependent increase in muscle fiber length and upregulation of regeneration‑related factors in primary skeletal muscle cells. Furthermore, C2C12 cells treated with rADAMTS‑1 exhibited enhanced expression of myocyte developmental genes during differentiation. The findings highlighted the therapeutic potential of rADAMTS‑1 for sarcopenia, potentially addressing limitations associated with conventional MuSC‑based treatments.