Connective Tissue Research最新文献

{"title":"\"The role of mitogen-activated protein kinase signaling pathway in bone formation during mid-palatal suture expansion\".","authors":"Xiaoyue Xiao, Shujuan Zou, Zhiai Hu, Jianwei Chen","doi":"10.1080/03008207.2025.2498509","DOIUrl":"https://doi.org/10.1080/03008207.2025.2498509","url":null,"abstract":"<p><strong>Purpose: </strong>Orthodontic interventions such as maxillary expansion are pivotal in correcting malocclusions; however, the intracellular mechanisms of bone remodeling during this process are not well understood. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in bone remodeling during maxillary expansion and relapse in rats.</p><p><strong>Materials and methods: </strong>Thirty male Wistar rats were randomly divided into three groups: Control (Ctrl), Expansion only (EO), and Expansion with MEK inhibitor U0126 (EO  +  INH). Customized expanders applied 100 g force for seven days, followed by natural relapse. Tissue changes within the mid-palatal suture were assessed via micro-computed tomography, histology, and immunohistochemistry. In vitro, primary bone marrow mesenchymal stem cells (BMSCs) were exposed to cyclic tensile stress with or without MAPK inhibition, followed by evaluation of protein expression, alkaline phosphatase activity, and Alizarin red staining.</p><p><strong>Results: </strong>The EO group showed a significant increase in maxillary arch width compared to the EO  +  INH group, a difference that remained significant after relapse. This group also had higher levels of phosphorylated mitogen-extracellular kinase (p-MEK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated Ets-like transcription factor 1 (p-ELK1), along with increased osteoblast markers and bone resorption. Conversely, MAPK inhibition impeded bone remodeling, indicated by decreased osteogenic markers and fewer TRAP-positive cells. In vitro, tensile stress enhanced osteogenic differentiation, which was attenuated with MAPK inhibition.</p><p><strong>Conclusions: </strong>Mechanical activation of MEK-ERK1/2-ELK1 pathway is essential for effective maxillary expansion. Thus, inhibiting this pathway significantly impairs bone remodeling, underscoring its potential as a therapeutic target to enhance bone formation in orthodontic treatments.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986405","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":"Clinical and molecular landscape of post-traumatic osteoarthritis.","authors":"Kyohei Takase, Patrick C McCulloch, Jasper H N Yik, Dominik R Haudenschild","doi":"10.1080/03008207.2025.2490797","DOIUrl":"https://doi.org/10.1080/03008207.2025.2490797","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown, chronic pain, and disability. Post-traumatic osteoarthritis (PTOA), a secondary form of OA, arises from joint injuries and consistently accounts for a proportion of symptomatic cases. Unlike primary OA, PTOA has a well-defined initiation point, presenting an opportunity for early intervention. Over the past two decades, research has shifted from a cartilage-centric view to a broader understanding of OA as a multifaceted disease involving inflammation, oxidative stress, and complex molecular crosstalk between chondrocytes, synoviocytes, osteocytes, and immune cells. Key inflammatory mediators, such as IL-1β, IL-6, TNF-α, and Wnt/β-catenin signaling, drive disease progression. Advances in imaging, biomarker discovery, and animal models have provided insights into early disease mechanisms. However, gaps remain in understanding the molecular events that trigger PTOA onset, the interplay between joint tissues, and the identification of reliable early biomarkers. Delayed diagnosis, lack of disease-modifying therapies, and OA's complexity remain critical barriers. Future directions should focus on precision medicine integrating biomarkers, imaging, and artificial intelligence for early diagnosis and risk stratification. Emerging regenerative and gene therapies, while promising, would benefit from moving beyond single-pathway targeting, as OA's multifaceted nature makes a combination approach desirable to simultaneously address inflammation, oxidative stress, cartilage matrix degradation, and tissue repair. Multidisciplinary collaborations between clinicians, molecular biologists, and bioengineers are essential to translating discoveries into effective interventions. A paradigm shift toward early, personalized treatment strategies is necessary to improve long-term outcomes in PTOA and OA management.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961864","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":"Mechanisms of anterior cruciate ligament injury-induced disruption of joint homeostasis and onset of osteoarthritis.","authors":"Robert H Brophy, Richard M Silverman, Muhammad Farooq Rai","doi":"10.1080/03008207.2025.2490097","DOIUrl":"https://doi.org/10.1080/03008207.2025.2490097","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a progressive joint disorder that leads to pain and disability for millions of people worldwide. Post-traumatic OA (PTOA), a form of OA, arises secondary to joint injury and often impacts younger individuals. Among the most common joint injuries leading to disrupted joint homeostasis and PTOA is anterior cruciate ligament (ACL) rupture. Even with successful surgical stabilization, the risk of developing PTOA persists due to several factors, including altered biology that contributes to disease progression. Recent research into the biology of ACL injuries has advanced our understanding of the mechanisms by which PTOA develops, including the inflammatory pathways involved, the expression of biomarkers specific to ACL injuries, and their interaction with factors such as the chronicity of the injury. Evidence suggests that homeostatic balance of anabolic and catabolic processes in the knee is disturbed after ACL tears, triggering a catabolic and degenerative phenotype, ultimately leading to premature joint degeneration, pain, and disability. Several key knowledge gaps exist, such as the determinants of the transition from acute to chronic inflammation, inter-patient variability in inflammatory responses, and influence of systemic factors on disease development. PTOA research faces numerous challenges, including protracted nature of the disease, the complexity of joint biology, and difficulties in translating molecular discoveries into clinical practice. Future research should prioritize improving biomarker precision for early detection, developing targeted therapies, and leveraging emerging technologies like machine learning to personalize treatment. This approach will enhance our understanding of the biological basis of PTOA resulting from ACL injuries and identify opportunities to mitigate the long-term consequences of these injuries.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983957","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":"Application of knee joint distraction: challenges and opportunities.","authors":"M P Jansen, S C Mastbergen","doi":"10.1080/03008207.2025.2490796","DOIUrl":"https://doi.org/10.1080/03008207.2025.2490796","url":null,"abstract":"<p><p>Knee osteoarthritis (OA) is a debilitating condition with limited treatment options beyond symptom management or total knee arthroplasty (TKA). For younger patients, TKA presents challenges, including higher failure rates and revision surgeries. Knee joint distraction (KJD) has emerged as a promising joint-preserving alternative for end-stage knee OA, demonstrating significant improvements in pain, function, and quality of life in clinical trials and clinical practice. Almost 20 years of research has highlighted KJD's capacity to delay or prevent TKA by promoting cartilage and subchondral bone repair through whole-joint remodeling. Recent studies, including a multicenter trial with a purpose-built distraction device, confirm the treatment's efficacy and durability, with benefits lasting up to 10 years. However, long-term outcomes remain limited, and variability in patient response underscores the need for refined predictive tools. Challenges include the high incidence of pin tract infections during treatment and integrating KJD into routine clinical practice, as highlighted by limited trial enrollment in the UK KARDS trial and variability in healthcare system compatibility. Future research should focus on minimizing complications, improving patient selection through advanced imaging and biomarker analyses, and further understanding the mechanisms underlying KJD-induced joint remodeling. Large-scale trials like the ongoing Dutch GODIVA study are poised to provide robust evidence for KJD's broader adoption, implementation, and reimbursement in healthcare systems. With continued advancements, KJD holds the potential to transform the management of knee OA, offering a viable alternative to TKA for younger patients and addressing a critical unmet need in OA care.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971571","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":"Biological impact of meniscus injury on post-traumatic osteoarthritis.","authors":"Nathan H Varady, Scott A Rodeo","doi":"10.1080/03008207.2025.2487916","DOIUrl":"https://doi.org/10.1080/03008207.2025.2487916","url":null,"abstract":"<p><p>Post-traumatic osteoarthritis (PTOA) is a common and debilitating problem following meniscal injury, which may lead to pain, loss of function, and early joint failure. Over the past 25 years, clinical, laboratory, and translational studies have greatly improved our understanding of PTOA pathogenesis and prevention. Clinical studies have established the benefit of meniscal preservation in preventing PTOA, leading to a significant increase in meniscus repair. Similarly, improved understanding of the biomechanical importance of the meniscal root attachment has increased focus on the detection and treatment of meniscal root injuries. Laboratory studies have demonstrated a preliminary mechanistic pathway of PTOA development following meniscal injury, whereby injury and altered joint loading stimulate a pro-inflammatory response that leads to both articular cartilage breakdown and impaired meniscal healing. In vitro evidence suggests that mechanical loading of the meniscus may ameliorate this catabolic response, with implications for treatment and rehabilitation protocols. Numerous animal models have emerged, allowing for in vivo assessment of PTOA initiation and offering a platform to test potential therapeutic targets. Despite these advances, meniscal repair remains imperfect and is not always possible, and investigations translating laboratory findings to the human setting have been limited. Future directions include further characterizing the immune and cellular responses to meniscal injury, investigating therapies to target the pro-inflammatory cascade and enhance meniscal healing, and developing new models to better distinguish PTOA pathogenesis in human subjects. Continued laboratory, translational, and clinical research efforts are required to identify treatment strategies to reduce the burden of PTOA after meniscal injury.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-6"},"PeriodicalIF":2.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984544","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":"LncRNA SNHG7 inhibits apoptosis and proliferation of osteoarthritis cells induced by IL-β through sponging miR-146b.","authors":"Naikai Lin, Zehui Song, Bitao Ma, Peng Wang","doi":"10.1080/03008207.2025.2487470","DOIUrl":"https://doi.org/10.1080/03008207.2025.2487470","url":null,"abstract":"<p><strong>Purpose: </strong>We probed the roles of SNHG7, miR-146b, PCBP1, and IL-β in the development of osteoarthritis (OA).</p><p><strong>Materials and methods: </strong>OA models were established using anterior cruciate ligaments, and chondrocytes were obtained from mouse cartilage tissue. Cells were treated with 10 ng/ml Il-1β. RT-qPCR was used to detect the expression of SNHG7, miR-146b, PCBP1, and IL-β in tissues and cells. Safranin-O/Fast Green staining was performed to analyze the cartilage damage in each group of mice.</p><p><strong>Results: </strong>SNHG7 and PCBP1 expressions were down-regulated, and miR-146b expression was up-regulated in OA tissue and IL-1β-treated chondrocytes compared to normal cartilage tissue and chondrocytes. Forced SNHG7 expression improved cartilage structure, enhanced proliferative viability of chondrocytes, and inhibited apoptosis and IL-1β release in IL-1β-treated chondrocytes in OA mice. In contrast, miR-146b upregulation decreased proliferative viability and promoted apoptosis and IL-1β release in chondrocytes. Rescue assays showed that miR-146b attenuated the protective effects of SNHG7 on apoptosis and inflammation in IL-1β-treated chondrocytes, and activation of PCBP1 expression significantly inhibited the cytotoxic effects of miR-146b. Mechanistically, SNHG7 acted as a competitive endogenous RNA by targeting miR-146b to promote the expression of PCBP1.</p><p><strong>Conclusions: </strong>This study confirms that SNHG7 inhibits IL-1β-mediated inflammatory responses in chondrocytes via the miR-146b/PCBP1 axis, thereby suppressing IL-1β-induced OA.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957784","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":"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}