Connective Tissue Research最新文献

{"title":"Metformin ablates high fat diet-induced skeletal muscle hypertrophy and elevation of sarcolemmal GLUT4 when feeding is initiated in young adult male mice.","authors":"John M Lawler, Khaled Y Kamal, Rachel E Botchlett, Shih Lung Woo, Honggui Li, Jeff M Hord, James D Fluckey, Chaodong Wu","doi":"10.1080/03008207.2025.2471853","DOIUrl":"10.1080/03008207.2025.2471853","url":null,"abstract":"<p><p>A high-fat diet (HFD) and metabolic disease can impair insulin signaling in skeletal muscle, including a reduction in IRS-1 and GLUT-4 at the cell membrane. Other sarcolemmal proteins (e.g. caveolin-3, nNOS) within the dystrophin-glycoprotein complex (DGC) are partially lost with Type II diabetes. Thus, we hypothesized that a HFD would cause a significant loss of sarcolemmal DGC proteins and GLUT4, and the anti-diabetic drug metformin would mitigate the disruption of the DGC and preserve sarcolemmal GLUT4 on the soleus muscle. Eight-week-old mice were fed a high-fat diet for 12 weeks. After 8 weeks, one-half of the HFD mice received metformin for the remaining 4 weeks. HFD caused a marked increase in soleus muscle mass and fiber cross-sectional area and elevated sarcolemmal GLUT4, even though systemic insulin resistance was greater. HFD-induced muscle hypertrophy and elevated membrane GLUT4 were unexpectedly attenuated by metformin. In addition, IRS-1 positive staining was not reduced by HFD but rather enhanced in the metformin mice fed a high-fat diet. Sarcolemmal staining of dystrophin and caveolin-3 was reduced by HFD but not in the metformin group, while nNOS intensity was unaffected by HFD and metformin. These findings suggest that skeletal muscles in young adult mice can compensate for a high-fat diet and insulin resistance, with a minor disruption of the DGC, by maintaining cell membrane nNOS and IRS-1 and elevating GLUT4. We postulate that a window of compensatory GLUT4 and nNOS signaling allows calorically dense food to enhance skeletal muscle fiber size when introduced in adolescence.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"121-135"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGF2BP3 facilitates the osteogenic differentiation of bone marrow mesenchyml stem cells via upregulating KLK4.","authors":"Jiazhu Tang, Guoyang Zhao, Jianzhong Zhao, Bo Wang","doi":"10.1080/03008207.2025.2458129","DOIUrl":"10.1080/03008207.2025.2458129","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP) is a chronic metabolic bone disease marked by imbalance in osteoblast and osteoclast activity. This study was aimed to explore the molecular mechanism underlying osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) to discover the novel target for OP.</p><p><strong>Methods: </strong>RT-qPCR was used for mRNA expression detection of Kallikrein 4 (KLK4) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). Protein detection was conducted by western blot. The osteogenic differentiation of BMSCs was evaluated through alkaline phosphatase (ALP) staining and Alizarin Red staining (ARS). Interaction between IGF2BP3 and KLK4 was analyzed using RNA immunoprecipitation (RIP) assay and actinomycin D assay.</p><p><strong>Results: </strong>KLK4 was downregulated in OP patients, and upregulated in osteogenically differentiated BMSCs. KLK4 overexpression promoted the osteogenic differentiation of BMSCs. IGF2BP3 enhanced the expression of KLK4. KLK4 upregulation restored the effect of IGF2BP3 knockdown on the osteogenic differentiation of BMSCs. Moreover, IGF2BP3 overexpression enhanced the osteogenic differentiation of BMSCs by promoting KLK4.</p><p><strong>Conclusion: </strong>These evidences suggested that IGF2BP3 contributed to the osteogenic differentiation of BMSCs via mediating KLK4, providing a potential target for treatment of OP.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 1","pages":"49-58"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Ketoglutarate promotes autophagic activity under a peri-implant condition to enhance osseointegration of dental implant in rats with osteoporosis.","authors":"Luyuan Chen, Qisen Li, Shengnan Ma, Bohua Wang","doi":"10.1080/03008207.2024.2442675","DOIUrl":"10.1080/03008207.2024.2442675","url":null,"abstract":"<p><strong>Aim: </strong>We aimed to investigate whether α-ketoglutarate (AKG) can promote autophagic activity under a peri-implant condition to enhance the osseointegration of dental implant in rats with osteoporosis (OP).</p><p><strong>Methods: </strong>Con, Model and AKG groups were established for the random allocation of thirty rats (<i>n</i> = 10). Their bone metabolism indicators were measured. The peri-implant bone morphology was detected by toluidine blue staining, the peri-implant bone tissue healing was detected, and the implant torque was measured.</p><p><strong>Results: </strong>In comparison to the Con group, the bone metabolism indicators [bone volume/tissue volume ratio (BV/TV), trabecular number (Tb.N), and osseointegration index (OI)], bone-implant contact (BIC) rate, bone mass in the cancellous area, dislocation torque, protein and mRNA expressions of bone morphogenetic protein-2 (BMP-2), RUNX2 and Beclin1, and LC3II/LC3I ratio in bone tissues decreased significantly in the Model group, with a significant enlargement of trabecular space (Tb.Sp) (<i>p</i> < 0.05). In comparison with the Model group, the AKG group had significant increases in Tb.N, BV/TV, OI, BIC rate, bone mass in the cancellous area, dislocation torque, mRNA plus protein expressions of BMP-2, Runt-related transcription factor 2 and Beclin1, and LC3II/light chain 3I ratio in bone tissues, in addition to a significant reduction of Tb.Sp (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>AKG may relieve the bone metabolism disorders and enhance the osteogenic differentiation and osseointegration of implants in OP rats by promoting peri-implant autophagy.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assembly of collagen fibers into contiguous dense and loose regions of subcutaneous fascia.","authors":"Natsuki Maeda, Takafumi Watanabe, Daisuke Suzuki, Tomohito Iwasaki, Yongchol Shin, Yasutada Imamura","doi":"10.1080/03008207.2025.2455730","DOIUrl":"10.1080/03008207.2025.2455730","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the collagen fiber structure of the subcutaneous fascia, a connective tissue layer between the skin and epimysium.</p><p><strong>Methods: </strong>Fascia samples with varying extensibility were examined using biochemical and microscopic methods.</p><p><strong>Results: </strong>Loose fascia, the more extensible type, displayed sparsely distributed collagen fibers, while dense fascia showed tightly packed collagen fiber bundles. Elastase treatment, after urea pretreatment, caused the loosening of collagen fiber bundles and increased collagen fiber generation as the treatment time increased. This suggests that elastic fibers contribute to collagen fiber bundle formation. Additionally, elastase treatment stretched the fascia, indicating the presence of twodimensional tensile stress generated by elastic fibers. Either enzymes capable of cleaving elastic fibers may be activated or the stretching of elastic fibers accompanying tissue deformation may increase the enzyme sensitivity to elastic fibers, leading to the formation of localized collagen fibers in vivo. Tissue staining confirmed that loose and dense fascia corresponded to areas with sparse and dense collagen fibers, respectively. Some dense collagen fibers appeared to migrate and disperse into loose areas.</p><p><strong>Conclusion: </strong>These findings provide insights into the structural organization and functional significance of collagen fibers within the subcutaneous fascia. They particularly highlight the role of elastic fibers in maintaining tissue integrity and facilitating dynamic remodeling.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"26-36"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allograft and autograft anterior cruciate ligament reconstructions exhibit a similar biological response to cyclic loading.","authors":"Lauren Paschall, Ariane Tsai, Erdem Tabdanov, Kara Negrini, Jenelle Izer, Aman Dhawan, Spencer E Szczesny","doi":"10.1080/03008207.2025.2456957","DOIUrl":"10.1080/03008207.2025.2456957","url":null,"abstract":"<p><strong>Objective: </strong>Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopaedic procedures. While outcomes are similar in the general patient population, the rerupture rate of non-irradiated allografts are 3-4 times higher than autografts in young active individuals. Previous studies suggest that the difference in clinical performance between graft types is due to impaired remodeling in allografts in response to loading. The objective of this study was to compare the remodeling response of autografts and allografts to cyclic loading. Furthermore, given that allografts are a foreign object and that immune cell signaling affects fibroblast mechanobiology, we compared markers of the immune cell composition between graft types.</p><p><strong>Methods: </strong>ACL reconstructions were performed on New Zealand white rabbits, harvested 8 weeks post-surgery, and cyclically loaded to 2 MPa in a tensile bioreactor. Expression of markers for anabolic and catabolic tissue remodeling, as well as inflammatory cytokines and immune cells, were quantified using quantitative reverse transcription polymerase chain reaction.</p><p><strong>Results: </strong>We found that the expression of markers for tissue remodeling were not different between allografts and autografts. Similarly, we found that the expression of markers for immune cells were not different between allografts and autografts.</p><p><strong>Conclusions: </strong>These data suggest that the poor clinical outcomes and impaired remodeling of allograft reconstructions compared to autografts is not due to a difference in graft mechanobiology.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 1","pages":"37-48"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of intramuscular administration of Platelet-Rich Plasma on denervated muscle after peripheral nerve injury.","authors":"Francisco Soldado, Maider López de Jesús, Maider Beitia, Imanol González-Burguera, Garazi Ocerin, Ainhoa Elejaga-Jimeno, Miquel Saumell-Esnaola, Sergio Barrondo, Jaime Oraa, Joan Sallés, Diego Delgado, Gontzal García Del Caño, Mikel Sánchez","doi":"10.1080/03008207.2024.2446888","DOIUrl":"10.1080/03008207.2024.2446888","url":null,"abstract":"<p><strong>Purpose: </strong>After peripheral nerve injury (PNI), prolonged denervation of the target muscle prevents adequate reinnervation even if the nerve is repaired. The aim of this work is to analyze the effect of intramuscular Platelet-Rich Plasma (PRP) in a denervated muscle due to PNI.Materials and.</p><p><strong>Methods: </strong>An irreversible PNI was generated in the common peroneal nerve of 80 Wistar rats by nerve resection. Animals were divided into groups: non-treatment (NT), saline (S) and PRP (PRP). 200 uL of saline (S group) and PRP (PRP group) were infiltrated intramuscularly into the tibialis anterior muscle on a weekly basis, from surgery to sacrifice (at 2, 4 and 7 weeks). Muscles were histologically processed for immunofluorescence and Western blotting. Effects on nicotinic acetylcholine receptor (nAChR), satellite cells (SC) and myogenin expression were analyzed. Comparisons were performed by two-way analysis of variance (ANOVA).</p><p><strong>Results: </strong>PRP had a platelet concentration 1.5-fold higher than blood, without erythrocytes and leukocytes. The PRP group had a higher percentage weight than the S and NT groups (<i>p</i> < 0.05). The levels of nAChRα1 and nAChRε subunit were lower in the PRP group relative to the NT and S (<i>p</i> < 0.05), while the nAChRγ subunit showed an increase in the PRP group (<i>p</i> < 0.05). The activation of SCs was higher in the PRP group compared to NT and S groups (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>PRP treatment can modulate NMJ configuration as well as key myogenic regulatory factors in denervated muscle, enhancing SC activation while mitigating muscle atrophy.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"10-25"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic characterization of particle-protein coronas shows differences between osteoarthritic and contralateral knees in a rat model.","authors":"Yash Y Shah, Brittany D Partain, Jessica L Aldrich, Michael Strinden, Jon Dobson, Carlos Rinaldi-Ramos, Kyle D Allen","doi":"10.1080/03008207.2025.2459242","DOIUrl":"10.1080/03008207.2025.2459242","url":null,"abstract":"<p><strong>Objective: </strong>When synthetic particles are injected into a biofluid, proteins nonspecifically adsorb onto the particle surface and form a protein corona. Protein coronas are known to alter how particles function in blood; however, little is known about protein corona formation in synovial fluid or how these coronas change with osteoarthritis (OA). In this study, protein coronas were characterized on particles incubated within OA-affected or healthy rat knees.</p><p><strong>Design: </strong>First, to evaluate particle collection techniques, magnetic polystyrene particles were placed in bovine synovial fluid and separated using either magnetics or centrifugation. In a second experiment, 12 male and 12 female Lewis rats received a simulated medial meniscal injury. At 2, 5, or 8 weeks post-surgery, operated and contralateral limbs were injected with clean magnetic particles (<i>n</i> = 8 per timepoint). After a 4-h incubation, animals were euthanized and particles were magnetically recovered. In both experiments, protein coronas were characterized using an Orbitrap fusion mass spectrometer.</p><p><strong>Results: </strong>In the first experiment, the particle separation method affected the identified proteins, likely due to centrifugation forces causing some large proteins to spin-down with the particles. In the OA model, 300-500 proteins were identified in the particle-protein coronas with 35, 59, and 13 proteins differing between the OA-affected and contralateral limbs at 2, 5, and 8 weeks, respectively. In particular, plectin, a serine (or cysteine) proteinase inhibitor, and cathepsin B were more prominent in the particle-protein coronas of OA-affected knees.</p><p><strong>Conclusions: </strong>Synthetic particles nonspecifically adsorb proteins in synovial fluid, and these binding events differ with OA severity.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 1","pages":"59-72"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic characterization of regenerated cartilage following knee joint distraction; a human case-study.","authors":"Jessica S J J Steijns, Daniel Green, Laura C W Peeters, Pieter J Emans, Tim A Boymans, Roderick H Stassen, Guus G H van den Akker, Andy Cremers, Liesbeth M C Jutten, James R Anderson, Mandy J Peffers, Marjolein M J Caron, Tim J M Welting","doi":"10.1080/03008207.2024.2440716","DOIUrl":"10.1080/03008207.2024.2440716","url":null,"abstract":"<p><strong>Purpose: </strong>Knee joint distraction is a surgical procedure with cartilage-regenerating properties. The composition of joint distraction-regenerated cartilage in human patients is poorly documented. In this case-study, provided a unique opportunity to biomolecularly characterize the regenerated tissue from a patient who underwent bilateral distraction and later knee replacements.</p><p><strong>Methods: </strong>Knee joint distraction was conducted using an external fixation frame and total knee arthroplasty was performed several years later. Radiographic imaging was performed to assess the status of the knee joint prior, during and after clinical interventions. Following total knee replacement, cartilage biopsies were collected and processed for tissue sectioning and histochemical staining. Tandem mass-spectrometry proteomics analysis was used to characterize and compare the proteomic composition.</p><p><strong>Results: </strong>Both knee joints showed joint-space improvement pre- and post-knee joint distraction. Regenerated cartilage was white with an irregular surface, while native (lateral) cartilage had a yellow appearance and smooth surface. Histochemical staining showed higher Safranin-O positivity in native cartilage compared to regenerated cartilage, and differences in collagen structure. Proteomic analysis did not reveal major differences in cartilage extracellular matrix protein abundance. Bioinformatic analyses revealed enrichment in ribosomal proteins (regenerated cartilage) and RNA Polymerase II Transcription Termination (native cartilage).</p><p><strong>Conclusion: </strong>Histologically, knee joint distraction-regenerated cartilage showed less glycosaminoglycans and disorganized collagen compared to native cartilage. However, mass-spectrometry has no major differences in extracellular matrix protein abundance, with proteomic clues suggesting protein translation regulation as a potential mechanism for regeneration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"486-496"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet-induced obesity exacerbated collagenase-induced tendon injury with upregulation of interleukin-1beta and matrix metalloproteinase-1.","authors":"Samuel Ka-Kin Ling, Zuru Liang, Pauline Po Yee Lui","doi":"10.1080/03008207.2024.2409751","DOIUrl":"10.1080/03008207.2024.2409751","url":null,"abstract":"<p><strong>Aims: </strong>Obesity increases tendinopathy's risk, but its mechanisms remain unclear. This study examined the effect of high-fat diet (HFD)-induced obesity on the outcomes and inflammation of collagenase-induced (CI) tendon injury.</p><p><strong>Methods: </strong>Mice were fed with standard chow (SC) or HFD for 12 weeks. Bacterial collagenase I or saline was injected over the patellar tendons of each mouse. At weeks 2 and 8 post-injection, the patellar tendons were harvested for histology, immunohistochemical staining, and gait analysis. The difference (Δ) of limb-idleness index (LII) at the time of post-injury and pre-injury states was calculated. Biomechanical test of tendons was also performed at week 8 post-injection.</p><p><strong>Results: </strong>HFD aggravated CI tendon injury with an increase in vascularity and cellularity compared to SC treatment. The histopathological score (week 2: <i>p</i> = 0.025; week 8: <i>p</i> = 0.013) and ΔLII (week 2: <i>p</i> = 0.012; week 8: <i>p</i> = 0.005) were significantly higher in the HFD group compared to those in the SC group after CI tendon injury. Stiffness (saline: <i>p</i> = 0.003; CI: <i>p</i> = 0.010), ultimate stress (saline: <i>p</i> < 0.001; CI: <i>p</i> = 0.006), and Young's modulus (saline: <i>p</i> = 0.017; CI: <i>p</i> = 0.007) were significantly lower in the HFD group compared to the SC group at week 8 after saline or collagenase injection. HFD induced higher expression of IL-1β (week 2: <i>p</i> = 0.010; week 8: <i>p</i> = 0.025) and MMP-1 (week 2: <i>p</i> = 0.010; week 8: <i>p</i> = 0.004) compared to SC treatment after CI tendon injury at both time points.</p><p><strong>Conclusions: </strong>HFD-induced obesity exacerbated histopathological, functional, and biomechanical changes in the CI tendon injury model, which was associated with an upregulation of IL-1β and MMP-1.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"447-457"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tendon-targeted knockout of collagen XI disrupts patellar and Achilles tendon structure and mechanical properties during murine postnatal development.","authors":"Jordan S Cohen, Ashley K Fung, Matthew K Stein, Christelle Darrieutort-Laffite, Stephanie N Weiss, Snehal S Shetye, Nat A Thurlow, Courtney A Nuss, Nathaniel A Dyment, Louis J Soslowsky","doi":"10.1080/03008207.2024.2432324","DOIUrl":"10.1080/03008207.2024.2432324","url":null,"abstract":"<p><strong>Background: </strong>Collagen XI is a fibril-forming collagen typically associated with type II collagen tissues but is also expressed in type I collagen-rich tendons, especially during development. We previously showed that tendon-targeted (Scx-Cre) Col11a1 knockout mice have smaller tendons in adulthood with aberrant fibril structure and impaired mechanical properties. However, the manifestation of this phenotype is not clearly understood. Therefore, our objective is to define the spatiotemporal roles of collagen XI in tendon structure-function during postnatal development. Given the high expression of collagen XI during embryonic development, we hypothesized that collagen XI knockout leads to the deposition of weakened extracellular matrix during early postnatal timepoints, disrupting the establishment of tendon structure and function.</p><p><strong>Methods: </strong>Patellar and Achilles tendons from postnatal (P) days 0, 10, 20, and 30 tendon-targeted scleraxis-Cre heterozygous and homozygous Col11a1 knockout mice were evaluated for morphology, nuclear organization, fibril morphology, mechanical properties, and gene expression.</p><p><strong>Results: </strong>At P0, there were no differences in tendon length or fibril diameter of either tendon. By P10, striking structural and functional differences emerged, with collagen XI deficiency resulting in increased tendon length, a heterogeneous and larger diameter population of fibrils, and inferior mechanical properties in both patellar and Achilles tendons. Differences increased in magnitude through P30, supporting our hypothesis that impaired structure-function during postnatal development may drive tendon lengthening and reduced mechanical properties.</p><p><strong>Conclusions: </strong>Though collagen XI is a quantitatively minor component of the tendon extracellular matrix, these results highlight the critical role of collagen XI in the acquisition of tendon structure-function.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"497-510"},"PeriodicalIF":2.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}