Matrix Biology Plus最新文献

{"title":"Loss of fibronectin fiber tension is inherent to ECM remodeling in human myocarditis and post-inflammatory fibrosis","authors":"Krishna Chander Sridhar ,&nbsp;Julia Mehl ,&nbsp;Karin Klingel ,&nbsp;Mario Thiele ,&nbsp;Sophie Van Linthout ,&nbsp;Carsten Tschöpe ,&nbsp;Georg N Duda ,&nbsp;Viola Vogel","doi":"10.1016/j.mbplus.2025.100182","DOIUrl":"10.1016/j.mbplus.2025.100182","url":null,"abstract":"<div><h3>Background</h3><div>Viral myocarditis (MC) is associated with extracellular matrix (ECM) remodeling and involves excessive deposition of collagen and other ECM proteins by cardiac fibroblasts, potentially leading to scarring and ECM stiffening, which may subsequently contribute to impaired cardiac functions. Clarifying whether changes in ECM fiber tension are detectable during either the acute or scarring phase could provide a novel, mechanistically relevant mechanobiological signature.</div></div><div><h3>Objectives</h3><div>Our goal was to ask whether ECM mechano-markers can be identified in the myocardium, beyond excessive collagen fiber deposition, that are associated with the acute infection or the pathological scarring of the human heart, and how this might be associated with the infiltration of macrophages.</div></div><div><h3>Methods</h3><div>Left-ventricular (LV) endomyocardial biopsies were obtained from patients (N = 39) with acute myocarditis MC (N = 21) including COVID-19 (N = 4) patients suspected with myocarditis MC and/or impaired LV function, dilated cardiomyopathy (N = 6), inflammatory dilated cardiomyopathy (N = 12) to specify diagnosis and treatment options. Endomyocardial biopsies were analyzed for viral genomes, immune cells infiltration and ECM remodeling. Fibronectin fiber tension was assessed using the fibronectin-binding tension-sensor (FnBPA5), while collagen fiber deposits were visualized using second harmonic generation (SHG) microscopy.</div></div><div><h3>Results</h3><div>While fibronectin fibers were tensed in healthy hearts, histological staining with our novel tension probe FnBPA5 showed that fibronectin fibers had lost their tension in distinct loci in all patient groups. In the acute inflammatory phase (MC), loci with untensed fibronectin fibers were found in close proximity to infiltrated macrophages. In already dilated hearts, biopsies which presented low densities of infiltrated macrophages, thick collagen I/III fiber bundles as visualized by SHG were found in proximity to untensed fibronectin fibers and myofibroblasts, which together are indicative of fibrotic ECM niches where the inflammation has subsided. Comparison of clinical diagnostic and experimental histological data showed clear correlations between altered ECM niche properties and cardiac function deterioration.</div></div><div><h3>Conclusions</h3><div>Our data suggest that relaxed fibronectin fibers are a recurrent feature of myocarditis and associate with measures of cardiac dysfunction. These findings suggest that fibronectin fiber tension might be a mechanobiological signature that warrants validation in larger, longitudinal cohorts and evaluation of in-vivo measurability.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"28 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome enriched serum enhances engineered ligament mechanics and collagen content with no additional benefit of resistance exercise.","authors":"Kevin J M Paulussen, Christopher M T Hayden, Taylor Griffin, Keith Baar","doi":"10.1016/j.mbplus.2025.100181","DOIUrl":"10.1016/j.mbplus.2025.100181","url":null,"abstract":"<p><p>Following resistance exercise, systemic changes foster improved functionality of tendons and ligaments. Post-exercise, muscle tissue releases exosomes that are thought to facilitate inter-tissue communication. To determine the potential role of exosomes in the exercise-induced adaptations of tendons and ligaments, we modified our engineered human ligament (EHL) model to work with exosome-enriched serum. Treatment of the EHLs with exosomes enriched from fetal bovine serum (fbEXO) resulted in enhanced ligament mechanics and increased collagen content in a dose-response fashion (maximum tensile load [MTL]: 10 %: 0.196 ± 0.138 N, 20 %: 0.278 ± 0.103 N, 40 %: 0.840 ± 0.092 N; r² = 0.858, <i>P</i> < 0.0001; collagen content: 10 %: 1.073 ± 12.49 µg, 20 %: 86.43 ± 71.65 µg, 40 %: 145.7 ± 84.11 µg; r² = 0.4735, <i>P</i> = 0.0046). After optimizing an exosome enriched feeding protocol using fbEXO, we confirmed that exosomes enriched from human serum (hsEXO) could sustain EHL function. Subsequently, twelve healthy, recreationally active volunteers (22 ± 3 y, 1,68 ± 0.10 m, 65.6 ± 27.8 kg; 6F/6M) performed a single bout of resistance exercise. Serum samples were collected prior to and 15 min post-exercise, and exosomes were enriched from these samples for treatment of EHLs. EHL function and collagen content did not differ when treated with hsEXO obtained at rest or post-resistance exercise (MTL: 1.30 ± 0.36 vs. 1.20 ± 0.36 N, <i>P</i> = 0.3950; collagen content: 424.6 ± 47.68 vs. 425.2 ± 44.46 µg, <i>P</i> = 0.9663). This model provides a novel way to determine the role of exosomes in connective tissue development and adaptation. The identification of circulating exercise factors that enhance tendon and ligament function remains to be fully elucidated.</p>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"27 ","pages":"100181"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic characterization of type I collagen N-terminal crosslinked peptides","authors":"Zsuzsanna Darula ,&nbsp;Maxwell C. McCabe ,&nbsp;Alex Barrett ,&nbsp;Lauren R. Schmitt ,&nbsp;Mark D. Maslanka ,&nbsp;Anthony J Saviola ,&nbsp;Joseph Orgel ,&nbsp;Alma Burlingame ,&nbsp;Claudia A. Staab-Weijnitz ,&nbsp;Kurt Stenmark ,&nbsp;Valerie Weaver ,&nbsp;Robert J. Chalkley ,&nbsp;Kirk C. Hansen","doi":"10.1016/j.mbplus.2025.100179","DOIUrl":"10.1016/j.mbplus.2025.100179","url":null,"abstract":"<div><div>Collagen cross-links mediated by the lysyl oxidase and lysyl hydroxylase families of enzymes significantly contribute to the biomechanical strength and rigidity of tissues, influencing cell signaling and the downstream cell phenotype. In the clinic, the proteolytically liberated N-terminal cross-linked peptide of collagen I (NTX) is used as a biomarker of bone and connective tissue turnover, which is altered in several disease processes. Despite the clinical utility of these collagen breakdown products, the majority of the cross-linked peptide species have not been identified in proteomic datasets. Here, we evaluate several parameters for the preparation and identification of these peptides from the collagen I-rich Achilles tendon. Our refined approach, which involves chemical digestion for protein solubilization coupled with mass spectrometry, enables the identification of NTX cross-links in a range of modification states. We then applied a spectral library approach to identify differences in collagen cross-links in bovine pulmonary hypertension. The presented method offers unique opportunities to understand extracellular matrix remodeling events in development, aging, wound healing, and fibrotic disease that modulate collagen architecture through lysyl hydroxylase and lysyl oxidase enzymes.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"27 ","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Proteomic profiling of the extracellular matrix in the human adrenal cortex” [Matrix Biology Plus 23 (2024) 100158]","authors":"Jean Lucas Kremer ,&nbsp;Henrique Sanchez Ortega ,&nbsp;Talita Souza-Siqueira ,&nbsp;Claudia Blanes Angeli ,&nbsp;Leo Kei Iwai ,&nbsp;Giuseppe Palmisano ,&nbsp;Claudimara Ferini Pacicco Lotfi","doi":"10.1016/j.mbplus.2025.100173","DOIUrl":"10.1016/j.mbplus.2025.100173","url":null,"abstract":"","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100173"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The staphylococcal collagen adhesin CNA35 effectively detects collagen and its fragments in blots after SDS-PAGE","authors":"Elena N. Pokidysheva ,&nbsp;Jennifer Diaz Sales ,&nbsp;Shinomi Yagi ,&nbsp;Tomonori Ueno ,&nbsp;Kanako Sasai ,&nbsp;Alice Makarenko ,&nbsp;Hans Peter Bächinger ,&nbsp;Kazunori Mizuno ,&nbsp;Sergei P. Boudko","doi":"10.1016/j.mbplus.2025.100174","DOIUrl":"10.1016/j.mbplus.2025.100174","url":null,"abstract":"<div><div>Collagens are a diverse family of proteins present in the extracellular matrix (ECM) of all animals. They play crucial roles in providing structural support to tissues, forming scaffolds for ECM suprastructures, and signaling cells. Certain collagen-binding proteins from pathogenic bacteria, such as CollageN Adhesin (CNA) from <em>Staphylococcus aureus</em>, interact with the collagen triple helix to promote host invasion. The extracellular portion of CNA, known as CNA35, which has a molecular weight of 35 kDa, has been used for <em>in vitro</em>, <em>ex vivo</em>, and <em>in vivo</em> staining of various collagen types in tissues.</div><div>Detecting various types of collagens necessitates the use of type- and specie-specific antibodies, which typically exhibit weak affinities for the triple helical regions of collagens. Additionally, the fragmentation of collagens can lead to a loss of detection due to the limited number of available epitopes. Furthermore, antibodies can be expensive, require secondary identification methods, and are often suitable for either immunohistochemistry or western blotting. Although successful procedures for staining collagens in tissues have been implemented, the detection of collagens and their fragments using CNA35 has not been reported for protein blots.</div><div>In this study, we examined the detection capabilities of a trimeric form of CNA35 for protein blots following SDS-PAGE. We successfully tested collagens I through VI, as well as fragments of collagen IV, under various conditions. Additionally, we investigated the impact of blocking solutions, incubation time, ligand concentration, and CNA35 concentration on sensitivity.</div><div>We achieved superior detection of all tested collagens and collagen IV fragments, including the 7S domain, which is a highly crosslinked complex composed of four triple-helical strands. The method we developed serves as a universal tool for detecting collagens and collagen-containing peptides in protein blots. It offers several advantages, including sub-nanogram sensitivity, low cost, and compatibility with standard western blotting techniques.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100174"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Integrin binding Ligand N-linked Glycoproteins, prostate-specific antigen and time to prostate cancer diagnosis","authors":"Alka Jain ,&nbsp;Ying Ni ,&nbsp;Daisy Zhang ,&nbsp;Eleanor M. Simonsick ,&nbsp;E. Jeffrey Metter ,&nbsp;Kalu U. Ogbureke ,&nbsp;Larry W. Fisher ,&nbsp;Neal S. Fedarko","doi":"10.1016/j.mbplus.2025.100171","DOIUrl":"10.1016/j.mbplus.2025.100171","url":null,"abstract":"<div><div>Background: <u>S</u>mall <u>I</u>ntegrin <u>B</u>inding <u>Li</u>gand <u>N</u>-linked <u>G</u>lycoproteins (SIBLINGs¹) were associated with cancer in cross-sectional studies. Whether SIBLINGs associate with preclinical disease is unknown. Methods: A retrospective longitudinal case control study was performed to determine the association of SIBLINGs and prostate-specific antigen (PSA) with preclinical disease. Paired serum samples from 109 cancer-free Baltimore Longitudinal Study on Aging participants were divided into those that were either most distal or proximal to diagnosis (cases) or censored (controls). Dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP), osteopontin (OPN), and PSA were measured by immunoassay and dichotomized into low or high based on their respective cut-off values. Associations of time to diagnosis or death, modeled as disease-free survival (DFS) or overall survival (OS), were assessed using Kaplan Meier and Cox proportional hazard survival estimates on individual and aggregated biomarkers in distal or proximal sets separately. Models were adjusted for relevant covariates. A false discovery rate analysis assessed significance of hazard ratios (HRs) in sets. Results: Biomarkers/aggregates identified as true discoveries for DFS included DSPP + PSA, OPN + PSA, DSPP + BSP + PSA, DSPP + OPN + PSA, where unadjusted distal HRs ranged between 11 and 27 and after adjusting for age from 7 to 15, while proximal HRs ranged between 6 and 10 unadjusted and 5 to 12 after adjusting for age. For proximal OS, true discoveries included DSPP + BSP, DSPP + OPN, DSPP + BSP + OPN, and DSPP + OPN + PSA where unadjusted HRs ranged between 6 and 20 while age-adjusted HRs ranged between 5 and 12. Conclusions: These observations support SIBLINGs as biomarkers that associate with DFS and OS in prediagnosis samples.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100171"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between T cells and fibroblasts in biomaterial-mediated fibrosis","authors":"Mathew Kibet,&nbsp;Daniel Abebayehu","doi":"10.1016/j.mbplus.2025.100172","DOIUrl":"10.1016/j.mbplus.2025.100172","url":null,"abstract":"<div><div>Biomaterial implants are a critical aspect of our medical therapies and biomedical research and come in various forms: stents, implantable glucose sensors, orthopedic implants, silicone implants, drug delivery systems, and tissue engineered scaffolds. Their implantation triggers a series of biological responses that often times lead to the foreign body response and subsequent fibrotic encapsulation, a dense ECM-rich capsule that isolates the biomaterial and renders it ineffective. These responses lead to the failure of biomaterials and is a major hurdle to overcome and in promoting their success. Much attention has been given to macrophage populations for the inflammatory component of these responses to biomaterials but recent work has identified an important role of T cells and their ability to modulate fibroblast activity and vice versa. In this review, we focus on T cell-fibroblast crosstalk by exploring T cell subsets, critical signaling pathways, and fibroblast populations that have been shown to dictate biomaterial-mediated fibrosis. We then highlight emerging technologies and model systems that enable new insights and avenues to T cell-fibroblast crosstalk that will improve biomaterial outcomes.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100172"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an in vitro platform for epithelial-stromal interactions: A basement membrane-containing scaffold from decellularized porcine bladders","authors":"J.A. Ramirez ,&nbsp;S. Estrada ,&nbsp;M.C. Harmsen ,&nbsp;P.K. Sharma","doi":"10.1016/j.mbplus.2025.100169","DOIUrl":"10.1016/j.mbplus.2025.100169","url":null,"abstract":"<div><div>The first organized extracellular matrix that appears during mammalian embryogenesis is a basement membrane (BM), BM is present in all adult epithelia, endothelia, muscle, nerve and fat tissues. BM is a sub-micrometer thick compact lattice of macromolecules that is maintained by the adhered cells. Systems such as collagen gels, Matrigel® or synthetic polymeric scaffolds have been proposed to mimic the BM and to study the interactions between different cell types, but all lack a structured BM. Here we aimed to obtain and characterize a natural, thin basement membrane-containing scaffold from pig urinary bladders that are subjected to blunt dissection of layers and decellularization steps, preserving the near native BM with a few layers of underlying connective tissue to maintain its structural integrity. The scanning electron microscopy, confocal multiphoton microscopy and immunohistochemistry helped confirm the presence of the BM. A veil-like network composed of thin fibers was present on top of a course network, and glycosaminoglycans, collagen and basement membrane proteins were present. The scaffold’s ability to repopulation and basement membrane barrier function were further confirmed when HaCaT and MRC5 cells attached and remained respectively on the epithelial and mesenchymal side without any crossover. Cells remained viable till 2 weeks. This BM-containing scaffold allows to create <em>in vitro</em> models of epithelial-mesenchymal tissues through a structured basement membrane and investigate basement membrane dynamics. The basement membrane-containing scaffold was found to be isotropic under uniaxial tension with a failure strain of 0.25 allowing its use to investigate strain induced basement membrane dynamics.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"26 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamically changing extracellular matrix stiffness drives Schwann cell phenotype","authors":"Alyssa Montgomery ,&nbsp;Jennifer Westphal ,&nbsp;Andrew E. Bryan ,&nbsp;Greg M. Harris","doi":"10.1016/j.mbplus.2024.100167","DOIUrl":"10.1016/j.mbplus.2024.100167","url":null,"abstract":"<div><div>Schwann cells (SCs) hold key roles in axonal function and maintenance in the peripheral nervous system (PNS) and are a critical component to the regeneration process following trauma. Following PNS trauma, SCs respond to both physical and chemical signals to modify phenotype and assist in the regeneration of damaged axons and extracellular matrix (ECM). There is currently a lack of knowledge regarding the SC response to dynamic, temporal changes in the ECM brought on by swelling and the development of scar tissue as part of the body’s wound-healing process. Thus, this work seeks to utilize a biocompatible, mechanically tunable biomaterial to mimic changes in the microenvironment following injury and over time. Previously, we have reported that ECM cues such as ligand type and substrate stiffness impact SC phenotype and plasticity, which was demonstrated by SCs on mechanically stable biomaterials. However, to better realize SC potential for plasticity following traumatic injury, a UV-tunable polydimethylsiloxane (PDMS) substrate with dynamically changing stiffness was utilized to mimic changes over time in the microenvironment. The dynamic biomaterial showed an increase in stress fibers, greater YAP expression, and fluctuations in c-Jun production in SCs in comparison to stiff and soft static controls. Utilizing biomaterials to better understand the role between temporal mechanical dynamics and SC phenotype holds a very high potential for developing future PNS therapies.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"25 ","pages":"Article 100167"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Cochlin drives impairments in tendon structure and function","authors":"Emmanuela Adjei-Sowah ,&nbsp;Elsa Lecaj ,&nbsp;Neeta Adhikari ,&nbsp;Clara Sensini ,&nbsp;Anne E.C. Nichols ,&nbsp;Mark R. Buckley ,&nbsp;Alayna E. Loiselle","doi":"10.1016/j.mbplus.2025.100168","DOIUrl":"10.1016/j.mbplus.2025.100168","url":null,"abstract":"<div><div>Aging tendons undergo disruptions in homeostasis, increased susceptibility to injury, and reduced capacity for healing. Exploring the mechanisms behind this disruption in homeostasis is essential for developing therapeutics aimed at maintaining tendon health through the lifespan. We have previously identified that the extracellular matrix protein, <em>Cochlin</em>, which is highly expressed in healthy flexor tendon, is consistently lost during both natural aging and upon depletion of Scleraxis-lineage cells in young animals, which recapitulates many aging-associated homeostatic disruptions. Therefore, we examined the effects of <em>Cochlin^-/-</em> on tendon maturation and hypothesized that loss of Cochlin would disrupt normal tendon maturation and recapitulate phenotypes associated with disrupted adult tendon homeostasis, including alterations in collagen fibril organization, and impaired tendon mechanics. By 3-months of age, <em>Cochlin^-/-</em> flexor tendons exhibited altered collagen structure, with these changes persisting through at least 9-months. In addition, Cochlin<em>^-/-</em> tendons demonstrated significant declines in structural and material properties at 6-months, and structural properties at 9-months. While <em>Cochlin^-/-</em> did not drastically change the overall tendon proteome, consistent decreases in proteins associated with RNA metabolism, extracellular matrix production and the cytoskeleton were observed in <em>Cochlin</em>^-/-. Interestingly, disrupted tendon maturation via <em>Cochlin^-/-</em> did not impair the tendon healing process. Taken together, these data define a critical role for Cochlin in facilitating physiological tendon maturation.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"25 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}