Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells
Year: 2026
Type: article
Abstract: This study shows that matrix metalloproteinase-10 (MMP-10) is a key regulator of satellite cell integrity and skeletal muscle homeostasis during aging. Using MMP-10 knockout mice, the authors demonstrate that loss of MMP-10 in young animals induces premature aging–like changes in muscle, including extracellular matrix (ECM) remodeling, increased DNA damage, activation of senescence pathways (p16INK4a/pRb), and functional decline of satellite cells. MMP-10 deficiency disrupts the structure of the satellite cell niche, altering collagen IV, fibronectin, laminin, and β-dystroglycan organization, which promotes early exit from quiescence, reduced self-renewal, accelerated differentiation, and increased susceptibility to senescence under proliferative stress. Mechanistically, quiescent satellite cells express little Mmp10 mRNA, but MMP-10 protein is present in the niche and becomes transcriptionally induced in activated satellite cells, fibro-adipogenic progenitors, and myoblasts after injury. In vitro silencing of MMP-10 accelerates satellite cell senescence, whereas exogenous MMP-10 delays senescence and reduces DNA damage. In dystrophic mdx mice, systemic MMP-10 treatment reduces muscle damage and improves satellite cell integrity. Together, the results identify MMP-10 as a critical extrinsic and intrinsic factor that preserves satellite cell function and delays muscle stem cell aging, highlighting MMP-10 as a potential therapeutic target in sarcopenia and muscular dystrophy.
Authors: Miriam Bobadilla, Josune Orbe, Gloria Abizanda, Florencio JD Machado, Amaia Vilas, Asier Ullate Agote, Leire Extramiana, Arantxa Baraibar Churio, Xabier L Aranguren, Gloria Cantero, Neira Sainz Amillo, José Antonio Rodríguez, Luis Ramos Garcia, Juan Pablo Romero Riojas, Ainara Vallejo Illarramendi, Carmen Paradas, Adolfo Lopez de Munain, José Antonio Páramo, Felipe Prósper, Ana Pérez Ruiz
Institutions: Centro de Investigación Médica Aplicada, Universidad de Navarra, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Clinica Universidad de Navarra, Biomedical Research Networking Center on Neurodegenerative Diseases, Biogipuzkoa Health Research Institute, Osakidetza
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7128616590
FWCI:
Cites:
Cited by:
Related to: