Connective Tissue Research最新文献

{"title":"Peripheral nerve repair using olfactory ensheathing and stem cells within a vein graft.","authors":"Brent A McMonagle","doi":"10.1080/03008207.2025.2466693","DOIUrl":"https://doi.org/10.1080/03008207.2025.2466693","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to assess nerve regeneration in vein grafts filled with olfactory ensheathing cells (OECs) or olfactory stem cells (ONSs) in a 15 mm gap male DA rat sciatic nerve model versus autografts.</p><p><strong>Methods: </strong>The control group (NG) received a nerve graft reversed and sutured into the 15 mm gap; all of the animals in the five experimental groups received a vein graft to bridge the 15 mm gap filled with extracellular matrix (ECM- MatrigelTM) only (VG); ECM with rat OECs suspended in ECM (VG + rOECs); ECM with human OECs (with Cyclosporin postoperatively to prevent graft rejection) (VG + hONS (c)); ECM only (with Cyclosporin postoperatively as a control for the previous group) (VG (c)); and ECM with rat ONSs within the vein grafts (VG + rONS). After 12 weeks ±4 days, electrophysiological analysis (latency and amplitude) and histological assessment of axon counts (immunohistochemistry with neurofilament [NF] stain) were undertaken.</p><p><strong>Results: </strong>Group VG + rOECs had the lowest latency results, NG had the highest amplitude results, and groups NG and VG + rOECs had significantly higher axon counts.</p><p><strong>Conclusions: </strong>The results trended toward the VG + rOECs and NG groups having the most successful electrophysiology results and axon counts. Incorporating OECs into vein grafts may be a viable alternative to nerve grafts for peripheral nerve repair.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794952","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":"Comparative characterization of hydrogels from human amniotic membrane and umbilical cord: biological and physicochemical properties.","authors":"Keykavos Gholami, Roham Deyhimfar, Ehsan Arefian, Matin Sadat Saneei Mousavi, Zahra Fekrirad, Parsa Nikoufar, Seyed Mohammad Kazem Aghamir","doi":"10.1080/03008207.2025.2483246","DOIUrl":"https://doi.org/10.1080/03008207.2025.2483246","url":null,"abstract":"<p><strong>Background: </strong>Various forms of decellularized extracellular matrix (dECM), including patches, powders, and hydrogels, have been applied to tissue engineering. Due to a broad need for alternatives to dECM, mostly derived from animal sources, human amniotic membrane (AM) and umbilical cord (UC) as disposable birthing materials can be suitable candidates. The present study developed hydrogels from AM and UC hydrogels and compared their physicochemical and biological properties.</p><p><strong>Materials and methods: </strong>The decellularized and powdered AM and UC tissues were solubilized with pepsin to form pre-gel solutions. The developed hydrogels underwent biological and physicochemical assessments using techniques such as western blot, scanning electron microscopy, immunohistochemistry, and histopathology.</p><p><strong>Results: </strong>UC hydrogel demonstrated a higher elastic modulus and shorter gelation time. Although the western blot results did not show significant differences in concentration of the main ECM components, specific staining showed a higher content of mucopolysaccharides in UC hydrogel as well as collagen fibers in AM hydrogel. Both hydrogels induced a fibroblast-like morphology in the cytoplasm of mesenchymal stromal cells (MSCs). Both hydrogels are suitable for 3D culture systems and support in vivo myogenic differentiation of MSCs. Finally, the hydrogels were found to be biocompatible in vivo and showed infiltration and colonization by host cells in mice.</p><p><strong>Conclusion: </strong>This study highlights significant bio-physicochemical variations between human UC and AM hydrogels, emphasizing the need for careful consideration in their application for tissue reconstruction, in vitro culture systems, and cell-delivery techniques.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729188","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":"The impact of N-acetylcysteine on early periods of tendon healing: <i>histopathologic, immunohistochemical, and biomechanical analysis in a rat model</i>.","authors":"Halil Büyükdoğan, Cemil Ertürk, Erdal Eren, Çiğdem Öztürk, Burak Yıldırım, Tahir Burak Sarıtaş, Metehan Demirkol","doi":"10.1080/03008207.2025.2479501","DOIUrl":"https://doi.org/10.1080/03008207.2025.2479501","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the early effects of N-acetylcysteine, which has antioxidant, inflame-modulatory, and cytoprotective properties, on tendon healing.</p><p><strong>Materials and methods: </strong>Thirty-five male Wistar Hannover rats were divided into five groups: first-week treatment (Group 1T), first-week control (Group 1C), third-week treatment (Group 3T), third-week control (Group 3C), and native tendons (Group N). Bilateral Achilles tenotomy was performed on all rats except Group N. After tenotomy, 150 mg/kg N-acetylcysteine was administered daily intraperitoneally to treatment groups, while isotonic saline was given to the control groups. Tendons were evaluated histopathologically, immunohistochemically, and biomechanically after sacrifice in the first and third weeks.</p><p><strong>Results: </strong>No significant differences were observed in the first week (<i>p</i> > 0.05). Movin and Bonar scores (lower scores reflect improved histologic healing) were significantly lower in Group 3T than in Group 3C (<i>p</i> = 0.002). Collagen type-I/type-III ratios were higher in Group 3T compared to Group 3C (<i>p</i> = 0.001). Fmax (N) values were similar across Group 3T, Group 3C, and Group N (<i>p</i> = 0.772). However, cross-sectional areas (mm²) were significantly smaller in Group 3T than in Group 3C (<i>p</i> = 0.001), with the smallest areas observed in native tendons. Thus, tensile strength (MPa, load per unit area) and toughness (J/10³ mm³, energy absorbed per unit volume) were significantly higher in Group 3T than in Group 3C (<i>p</i> = 0.001).</p><p><strong>Conclusion: </strong>N-acetylcysteine supplied some improved results on early markers of tendon healing. Although our findings support the potential of NAC as a therapeutic adjunct in tendon injuries, further studies are needed to evaluate the long-term effects and underlying mechanisms.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.8,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676770","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":"Mechanism of IRF8 on osteocyte apoptosis in steroid-induced osteonecrosis of the femoral head.","authors":"Junwu Ye, Tianmin Chang, Xihai Zhang, Daiqing Wei, Yuanhui Wang","doi":"10.1080/03008207.2025.2472935","DOIUrl":"10.1080/03008207.2025.2472935","url":null,"abstract":"<p><strong>Background: </strong>Steroid-induced osteonecrosis of the femoral head (SONFH) is a metabolic disorder that leads to structural changes, collapse of the femoral head, and joint dysfunction. This study investigates the role of interferon regulatory factor 8 (IRF8) in osteocyte apoptosis in SONFH, so as to find new targets for the treatment of SONFH.</p><p><strong>Methods: </strong>Murine long bone osteocyte-Y4 cells were cultured and treated with dexamethasone to establish SONFH cell models. si-IRF8 was transfected into the cells. The expression levels of IRF8, B cell leukemia/lymphoma 2 (Bcl-2), BCL2 associated X (Bax), zinc finger protein 667 (ZNF667), and miR-181a-5p were detected. Cell apoptosis and viability were detected. The enrichment of IRF8 on the miR-181a-5p promoter was assayed. The binding relationship between IRF8 and miR-181a-5p promoter, and between miR-181a-5p and ZNF667 3'UTR sequence was verified. Combined experiments with miR-181a-5p knockdown or ZNF667 overexpression were performed to observe the changes in cell apoptosis.</p><p><strong>Results: </strong>IRF8 and ZNF667 were increased in SONFH cells and miR-181a-5p was decreased. Inhibition of IRF8 increased SONFH cell viability and reduced apoptosis. Mechanistically, IRF8 was enriched in the miR-181a-5p promoter to inhibit miR-181a-5p and miR-181a-5p targeted and inhibited ZNF667. miR-181a-5p knockdown or ZNF667 overexpression could alleviate the inhibitory effect of IRF8 down-regulation on osteocyte apoptosis in SONFH.</p><p><strong>Conclusion: </strong>IRF8 was enriched in the miR-181a-5p promoter to inhibit miR-181a-5p, thus promoting ZNF667 levels and increasing osteocyte apoptosis in SONFH, which may be a new theoretical basis for the treatment of SONFH.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"136-146"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584705","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":"Correction.","authors":"","doi":"10.1080/03008207.2025.2483579","DOIUrl":"10.1080/03008207.2025.2483579","url":null,"abstract":"","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"147"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691387","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":"Lysophosphatidic acid regulates implant osseointegration in murine models via YAP.","authors":"Qin Zhang, Ying Yuan, Bin Wang, Ping Gong, Lin Xiang","doi":"10.1080/03008207.2025.2459856","DOIUrl":"10.1080/03008207.2025.2459856","url":null,"abstract":"<p><strong>Background: </strong>Lysophosphatidic acid (LPA), a simple bioactive lysophospholipid, has been reported to regulate bone homeostasis and bone remodeling. This study aimed to elucidate the function and intrinsic mechanism of LPA in osseointegration in murine models.</p><p><strong>Method: </strong>We constructed immediate implant models in murine maxillae. Micro-CT, H&E staining, and PCR assays were performed to evaluate the effects of LPA on osseointegration. Furthermore, <i>Prx1-Cre;Yap^f/f</i> mice and <i>Sp7-Cre;Yap^f/f</i> mice were generated to investigate the role of YAP on LPA-induced osseointegration.</p><p><strong>Result: </strong>In this study, we identified that LPA might promote bone deposition on the tissue-implant interface and improve osseointegration. In addition, conditional knockout of YAP from MCSs and pre-osteoblasts blunts LPA-induced osteogenesis and osseointegration in mice.</p><p><strong>Conclusion: </strong>Our data demonstrated that LPA-YAP signaling is particularly important to regulate osseointegration, which expands our understanding of LPA and provide the potential of LPA to be used in osseointegration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"87-95"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187674","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":"Functional changes to Achilles tendon and enthesis in an adolescent mouse model of testosterone hormone therapy.","authors":"LeeAnn A Hold, Tessa Phillips, Paige Cordts, Stephanie S Steltzer, Seung-Ho Bae, Brandon W Henry, Nicole Migotsky, Sydney Grossman, Cynthia Dela Cruz, Vasantha Padmanabhan, Molly B Moravek, Ariella Shikanov, Adam C Abraham, Megan L Killian","doi":"10.1080/03008207.2025.2465322","DOIUrl":"10.1080/03008207.2025.2465322","url":null,"abstract":"<p><strong>Purpose/aim: </strong>Some youth seek puberty suppression to prolong decision-making prior to starting hormone therapy to help align their physical sex characteristics with their gender identity. During peripubertal growth, connective tissues such as tendon rapidly adapt to applied mechanical loads (e.g. exercise) yet if and how tendon adaptation is influenced by sex and gender-affirming hormone therapy during growth remains unknown. The goal of this study was to understand how pubertal suppression followed by testosterone influences the structural and functional properties of the Achilles tendon using an established adolescent mouse model of testosterone hormone therapy.</p><p><strong>Materials and methods: </strong>C57BL/6N female mice were assigned at postnatal day 26 to the following experimental groups: control (vehicle treated), gonadotropin release hormone analogue (GnRHa) treatment alone to delay puberty, testosterone (T) alone after puberty, or delayed puberty with T treatment (i.e. GnRHa followed by T).</p><p><strong>Results: </strong>We found that pubertal suppression using GnRHa with and without T, as well as treatment with T alone post-puberty, increased the ultimate load of tendon in female mice. Additionally, we found that GnRHa, but not T treatment resulted in a significant increase in cell density at the Achilles enthesis.</p><p><strong>Conclusions: </strong>These findings demonstrate that delayed puberty and T have no negative influence on structural or functional properties of mouse tendon.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"96-106"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522759","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":"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":"TGF-β1 requires IL-13 to sustain collagen accumulation and increasing tissue strength and stiffness.","authors":"Caitlin M Hopkins, Benjamin T Wilks, Jeffrey R Morgan","doi":"10.1080/03008207.2025.2469575","DOIUrl":"10.1080/03008207.2025.2469575","url":null,"abstract":"<p><strong>Aims: </strong>Fibrosis is a multifactorial process characterized by the excessive accumulation of extracellular matrix (ECM), increased tissue stiffness, and decreased elasticity. This study examined how individual cytokines and a cytokine combination alter collagen production and biomechanics in a 3D in vitro model of the human ECM.</p><p><strong>Methods: </strong>Cultured human fibroblasts were seeded into a circular agarose trough molded in 24 well plates. The fibroblasts aggregated and formed a 3D ring-shaped tissue that synthesized de novo a collagen-rich human ECM complete with collagen fibrils. Unlike existing models, no macromolecular crowders were added, nor artificial scaffolds or exogenous ECM proteins. Rings were treated with TGF-β1, IL-13 or the combination of TGF-β1 and IL-13 for up to 3 weeks. Morphology, histology, collagen, DNA, fibril formation, gene expression and tensile properties of the rings were measured.</p><p><strong>Results: </strong>As the rings compacted, cellularity and total DNA decreased, whereas total collagen accumulated. TGF-β1 stimulated collagen accumulation and increased ring biomechanics at day 7, but these increases stalled and declined by day 21. When treated with IL-13, a cytokine exclusive to the immune system, there were no significant differences from control. However, when TGF-β1 was combined with IL-13, collagen levels and ring biomechanics increased over the entire three weeks to levels higher than TGF-β1 alone. Gene expression was differentially regulated by cytokine treatment over the entire three weeks suggesting that increased collagen accumulation was not due to upregulation of collagen gene expression.</p><p><strong>Conclusions: </strong>These results suggest that TGF-β1 requires a second signal, such as IL-13, to sustain the long-term pathological increases in collagen accumulation and biomechanics that can compromise the function of fibrotic tissues.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"107-120"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514957","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":"Creatine promotes osteogenic differentiation of dental pulp stem cells via the AMPK-ULK1-autophagy axis.","authors":"Lin Liu, Zhuangzhuang Chu, Xiao Han, Jin Wu, Kunzhan Cai, Jiaohong Wang, Zixiang Guo, Shan Gao, Guoqing Li, Chunbo Tang","doi":"10.1080/03008207.2025.2459243","DOIUrl":"10.1080/03008207.2025.2459243","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs.</p><p><strong>Materials and methods: </strong>HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related protein marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo.</p><p><strong>Results: </strong>We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis.</p><p><strong>Conclusion: </strong>Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"73-86"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390233","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}