{"doi":"10.1101/2022.10.31.514525","title":"The extracellular matrix differentially directs myoblast motility in distinct forms of muscular dystrophy","abstract":"ABSTRACT Extracellular matrix (ECM) pathologic remodeling underlies many fibrotic disorders, including muscular dystrophy. Tissue decellularization removes cellular components while leaving behind ECM components. We generated “on-slide” decellularized tissue slices from genetically distinct dystrophic mouse models. The ECM of dystrophin-and sarcoglycan-deficient muscles had marked thrombospondin 4 deposition, while dysferlin-deficient muscle had excess decorin. Annexins A2 and A6 were present on all dystrophic decellularized ECMs, but annexin matrix deposition was excessive in dysferlin-deficient muscular dystrophy. Adeno-associated viral expression of annexin A6 specifically in muscle resulted in annexin A6 deposition throughout the ECM, indicating muscle as a source of this ECM protein. C2C12 myoblasts seeded onto decellularized matrices displayed differential myoblast mobility. Dystrophin-deficient decellularized matrices inhibited myoblast mobility while dysferlin-deficient decellularized matrices enhanced myoblast movement. Myoblasts treated with recombinant annexin A6 increased mobillity similar to that seen on dysferlin-deficient decellularized matrix. These findings demonstrate specific fibrotic signatures elicit effects on myoblast activity. TEASER Fibrosis in muscular dystrophy has differential effects on myoblasts HIGHLIGHTS Spatial architecture and composition of the ECM differ across genetically distinct forms of muscular dystrophy, especially with respect to Annexin A6 protein deposition Matrix from dystrophin-mediated muscular dystrophy inhibits myoblast movement Matrix from dysferlin-deficient muscular dystrophy promotes myoblast motility Annexin A6 was sufficient to enhance myoblast motility","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312741,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1011047,"name":"Jason M. Kwon","orcid":null,"position":1,"is_corresponding":false},{"id":647813,"name":"GaHyun Lee","orcid":"0000-0002-8000-4663","position":2,"is_corresponding":false},{"id":554011,"name":"Nina L. Reiser","orcid":"0000-0002-4331-163X","position":3,"is_corresponding":false},{"id":554010,"name":"Lauren A. Vaught","orcid":"0000-0001-8634-9139","position":4,"is_corresponding":false},{"id":1010599,"name":"Joseph O’Brien","orcid":"0000-0003-3814-3608","position":5,"is_corresponding":false},{"id":930862,"name":"Patrick Page","orcid":"0000-0001-5805-2063","position":6,"is_corresponding":false},{"id":872581,"name":"Michele Hadhazy","orcid":"0000-0001-7446-7824","position":7,"is_corresponding":false},{"id":987288,"name":"Joseph C. Reynolds","orcid":"0000-0002-1931-4814","position":8,"is_corresponding":false},{"id":244630,"name":"Rachelle H. Crosbie","orcid":"0000-0001-6630-6713","position":9,"is_corresponding":false},{"id":554009,"name":"Alexis R. Demonbreun","orcid":"0000-0001-6823-125X","position":10,"is_corresponding":false},{"id":297686,"name":"Elizabeth M. McNally","orcid":"0000-0002-1221-719X","position":11,"is_corresponding":false},{"id":930860,"name":"Ashlee M. Long","orcid":"0000-0001-9380-3395","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T00:33:40.460845Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}