Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Ainara Vallejo-Illarramendi¹  Adolfo López de Munain²  Gloria Cantero³  Carmen Paradas³  Florencio J. D. Machado⁴  José Antonio Rodríguez⁵  José Antonio Páramo⁶  Josune Orbe⁷  Luis Ramos García⁸  Neira Sáinz Amillo⁹  Juan Pablo Romero Riojas^1,10  Leire Extramiana^1,10  Asier Ullate-Agote^1,10  Ana Pérez-Ruiz^1,10  Arantxa Baraibar Churio^1,10  Gloria Abizanda^1,10  Xabier L. Aranguren^1,10  Miriam Bobadilla Muñoz^1,10  Amaia Vilas^1,10  Felipe Prósper^1,11 

[1] CIBERNED-Biodonostia, Neurosciences Area, Group of Neuromuscular Diseases, San Sebastian, Spain;CIBERNED-Biodonostia, Neurosciences Area, Group of Neuromuscular Diseases, San Sebastian, Spain;Neurology Department, Osakidetza Basque Health Service, Donostialdea Integrated Health Organisation, San Sebastian, Spain;Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Neuromuscular Disorders Unit, Sevilla, Spain;Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain;Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain;Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain;Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain;Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain;Hematology Service, Clínica Universidad de Navarra, Pamplona, Spain;Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain;Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS)-Ictus, Instituto de Salud Carlos III, Madrid, Spain;Radiology Department, Clínica Universidad de Navarra, Pamplona, Spain;Radiology Department, Osakidetza Basque Health Service, Donostialdea Integrated Health Organisation, San Sebastian, Spain;Regenerative Medicine Program, Center for Applied Medical Research (CIMA) Universidad de Navarra, CIBERONC, Madrid, Spain;Centre for Nutrition Research, Universidad de Navarra, Pamplona, Spain;Regenerative Medicine Program, Center for Applied Medical Research (CIMA) Universidad de Navarra, CIBERONC, Madrid, Spain;Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;Regenerative Medicine Program, Center for Applied Medical Research (CIMA) Universidad de Navarra, CIBERONC, Madrid, Spain;Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain;Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA Universidad de Navarra, Pamplona, Spain;

关键词: MMP-10;    satellite cell;    muscle repair;    DNA damage;    aging;    senescence;    ECM;   

DOI  :  10.3389/fcell.2023.1128534

 received in 2022-12-20, accepted in 2023-04-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

Aged muscles accumulate satellite cells with a striking decline response to damage. Although intrinsic defects in satellite cells themselves are the major contributors to aging-associated stem cell dysfunction, increasing evidence suggests that changes in the muscle-stem cell local microenvironment also contribute to aging. Here, we demonstrate that loss of the matrix metalloproteinase-10 (MMP-10) in young mice alters the composition of the muscle extracellular matrix (ECM), and specifically disrupts the extracellular matrix of the satellite cell niche. This situation causes premature features of aging in the satellite cells, contributing to their functional decline and a predisposition to enter senescence under proliferative pressure. Similarly, reduction of MMP-10 levels in young satellite cells from wild type animals induces a senescence response, while addition of the protease delays this program. Significantly, the effect of MMP-10 on satellite cell aging can be extended to another context of muscle wasting, muscular dystrophy. Systemic treatment of mdx dystrophic mice with MMP-10 prevents the muscle deterioration phenotype and reduces cellular damage in the satellite cells, which are normally under replicative pressure. Most importantly, MMP-10 conserves its protective effect in the satellite cell-derived myoblasts isolated from a Duchenne muscular dystrophy patient by decreasing the accumulation of damaged DNA. Hence, MMP-10 provides a previously unrecognized therapeutic opportunity to delay satellite cell aging and overcome satellite cell dysfunction in dystrophic muscles.

【 授权许可】

Unknown   
Copyright © 2023 Bobadilla Muñoz, Orbe, Abizanda, Machado, Vilas, Ullate-Agote, Extramiana, Baraibar Churio, Aranguren, Cantero, Sáinz Amillo, Rodríguez, Ramos García, Romero Riojas, Vallejo-Illarramendi, Paradas, López de Munain, Páramo, Prósper and Pérez-Ruiz.