Achilles tendon; fatty infiltration; muscle force; muscular degeneration; satellite cells; second-harmonic generation microscopy; Medicine (miscellaneous); Biochemistry, Genetics and Molecular Biology (all); General Biochemistry, Genetics and Molecular Biology
Abstract :
[en] Achilles tendon rupture is a frequent injury with an increasing incidence. After clinical surgical repair, aimed at suturing the tendon stumps back into their original position, the repaired Achilles tendon is often plastically deformed and mechanically less strong than the pre-injured tissue, with muscle fatty degeneration contributing to function loss. Despite clinical outcomes, pre-clinical research has mainly focused on tendon structural repair, with a lack of knowledge regarding injury progression from tendon to muscle and its consequences on muscle degenerative/regenerative processes and function. Here, we characterize the morphological changes in the tendon, the myotendinous junction and muscle belly in a mouse model of Achilles tendon complete rupture, finding cellular and fatty infiltration, fibrotic tissue accumulation, muscle stem cell decline and collagen fiber disorganization. We use novel imaging technologies to accurately relate structural alterations in tendon fibers to pathological changes, which further explain the loss of muscle mechanical function after tendon rupture. The treatment of tendon injuries remains a challenge for orthopedics. Thus, the main goal of this study is to bridge the gap between clinicians' knowledge and research to address the underlying pathophysiology of ruptured Achilles tendon and its consequences in the gastrocnemius. Such studies are necessary if current practices in regenerative medicine for Achilles tendon ruptures are to be improved.
Gil-Melgosa, Lara ; Orthopedic Surgery Department, Clínica Universidad de Navarra (CUN), 31008 Pamplona, Spain ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Grasa, Jorge ; Aragón Institute of Engineering Research (I3A), University of Zaragoza, 50018 Zaragoza, Spain ; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
Urbiola, Ainhoa; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain ; Imaging Platform, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain
Llombart, Rafael ; Orthopedic Surgery Department, Clínica Universidad de Navarra (CUN), 31008 Pamplona, Spain ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Susaeta Ruiz, Miguel ; Université de Liège - ULiège > GIGA ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Montiel, Verónica ; Orthopedic Surgery Department, Clínica Universidad de Navarra (CUN), 31008 Pamplona, Spain ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Ederra, Cristina; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain ; Imaging Platform, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain
Calvo, Begoña ; Aragón Institute of Engineering Research (I3A), University of Zaragoza, 50018 Zaragoza, Spain ; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain
Ariz, Mikel; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain ; Imaging Platform, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain
Ripalda-Cemborain, Purificación; Orthopedic Surgery Department, Clínica Universidad de Navarra (CUN), 31008 Pamplona, Spain ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Prosper, Felipe ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain ; Haematology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain
Ortiz-de-Solórzano, Carlos ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain ; Imaging Platform, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain
Pons-Villanueva, Juan ; Orthopedic Surgery Department, Clínica Universidad de Navarra (CUN), 31008 Pamplona, Spain ; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Pérez Ruiz, Ana; Regenerative Medicine Program, Foundation for Applied Medical Research (FIMA), University of Navarra (UNAV), 31008 Pamplona, Spain ; Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain
Funding: Research support was provided by the Spanish Ministerio de Ciencia, Innovación y Univer-sidades (Grant PID2020-113822RB-C21 & PID2020-113822RB-C22) and the Department of Industry and Innovation (Government of Aragon) through the research group Grant T24-20R (cofinanced by Feder). Part of the work was performed by the ICTS “NANBIOSIS” specifically by the Tissue & Scaffold Characterization Unit (U13) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN at the University of Zaragoza). CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. C.O.-d.-S. acknowledges funding project RTI2018-094494-B-C22 financed by MCIN/AEI /10.13039/501100011033 and FEDER Funds.We especially thank Carolina Jorrin for magnificent technical support. We thank DSHB for the antibodies used in this study. Research support was provided by the Spanish Ministerio de Ciencia, Innovación y Universidades (Grant PID2020-113822RB-C21 & PID2020-113822RB-C22) and the Department of Industry and Innovation (Government of Aragon) through the research group Grant T24-20R (cofinanced by Feder). Part of the work was performed by the ICTS “NANBIOSIS” specifically by the Tissue & Scaffold Characterization Unit (U13) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN at the University of Zaragoza). CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. C.O.-d.-S. acknowledges funding project RTI2018-094494-B-C22 financed by MCIN/AEI /10.13039/501100011033 and FEDER Funds.
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