Connective Tissue Research最新文献

{"title":"Preliminary study of extracorporeal shock wave alleviating joint capsule fibrosis caused by internal bleeding of knee joint in rats.","authors":"Lei Huo, Quan-Bing Zhang, De-Ting Zhu, Kui Wang, Zun-Yu Du, Xue-Ming Li, Jing Mao, Xiu-Li Kan, Run Zhang, Yun Zhou","doi":"10.1080/03008207.2024.2387729","DOIUrl":"10.1080/03008207.2024.2387729","url":null,"abstract":"<p><strong>Purpose: </strong>Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats.</p><p><strong>Methods: </strong>Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group's knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, β-catenin protein expression in joint capsule using Western blotting.</p><p><strong>Results: </strong>Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, β-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased.</p><p><strong>Conclusions: </strong>Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"397-406"},"PeriodicalIF":2.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975317","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":"Transcriptome sequencing reveals inflammation and macrophage heterogeneity in subacromial bursa from degenerative shoulder disorders.","authors":"Jiabao Ju, Mingtai Ma, Yichong Zhang, Zhentao Ding, Pingping Lin, Jianhai Chen","doi":"10.1080/03008207.2024.2386548","DOIUrl":"10.1080/03008207.2024.2386548","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to investigate the transcriptomic alterations that occur in the subacromial bursa (SAB) following degenerative or traumatic shoulder diseases.</p><p><strong>Materials and methods: </strong>RNA sequencing was employed to evaluate the transcriptomic alterations of the SAB in individuals afflicted with degenerative rotator cuff tear (RCT), traumatic RCT and proximal humerus fracture (PHF). To gain insights into the biological significance of differentially expressed genes (DEGs), we conducted an enrichment analysis utilizing Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We further utilized single-cell RNA sequencing datasets of SAB from a recently published study to explore the associated cellular dynamics and alterations.</p><p><strong>Results: </strong>We detected 1,790 up-regulated and 1,964 down-regulated DEGs between degenerative RCT and PHF, 2,085 up-regulated and 1,919 down-regulated DEGs between degenerative RCT and traumatic RCT, and 20 up-regulated and 12 down-regulated DEGs between traumatic RCT and PHF. Given the similar expression pattern between traumatic RCT and PHF, they were integrated as the traumatic group. In comparison with the traumatic group, 1,983 up-regulated and 2,205 down-regulated DEGs were detected in degenerative SAB. Enrichment analysis of up-regulated DEGs uncovered an elevated inflammatory and immunologic responses in degenerative SAB. Single-cell transcriptomic analysis revealed macrophage represented the immune cell with the most DEGs between the degenerative and traumatic RCT.</p><p><strong>Conclusion: </strong>Our results revealed that the SAB in degenerative RCT exhibited a different transcriptional signature compared to that in traumatic RCT, and enrichment analysis showed immunologic and inflammatory activations. Macrophages may play a fundamental role in this process.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"383-396"},"PeriodicalIF":2.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897007","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":"Ubiquitin C-terminal hydrolase L1 activation in periodontal ligament cells mediates orthodontic tooth movement via the MAPK signaling pathway.","authors":"Fu Zheng, Feifei Wang, Tong Wu, Hongyi Tang, Huazhi Li, Xinyu Cui, Cuiying Li, Jiuhui Jiang","doi":"10.1080/03008207.2024.2395998","DOIUrl":"10.1080/03008207.2024.2395998","url":null,"abstract":"<p><strong>Purpose: </strong>Periodontal ligament cells (PDLCs) play a significant role in orthodontic force induced bone remodeling. However, the molecular mechanisms by which PDLCs respond to mechanical stimuli and influence osteoclastic activities remain unclear. This study aims to investigate the role of UCHL1, a key deubiquitinating enzyme involved in protein degradation and cellular responses, in force-treated PDLCs during orthodontic tooth movement (OTM).</p><p><strong>Materials and methods: </strong>In this study, we conducted <i>in vivo</i> and <i>in vitro</i> experiments using human PDLCs and a rat model of OTM. Mechanical stress was applied to PDLCs, and UCHL1 expression was analyzed through quantitative real-time polymerase chain reaction (qPCR), Western blot, and immunofluorescence staining. UCHL1 knockdown was achieved using siRNA, and its effects on osteoclast differentiation were assessed. The role of the MAPK/ERK pathway was investigated using the MEK-specific inhibitor U0126. An animal model of OTM was established, and the impact of UCHL1 inhibitor-LDN57444 on OTM and osteoclastic activity was evaluated through micro-CT analysis, histological staining, and immunohistochemistry.</p><p><strong>Results: </strong>Mechanical force induced UCHL1 expression in PDLCs during OTM. UCHL1 knockdown downregulated the RANKL/OPG ratio in PDLCs, affecting osteoclast differentiation. LDN57444 inhibited OTM and osteoclastic activity. UCHL1 activation correlated with ERK1/2 phosphorylation in force-treated PDLCs.</p><p><strong>Conclusions: </strong>Mechanical force mediated UCHL1 activation in PDLCs promotes osteoclast differentiation via the ERK1/2 signaling pathway during OTM.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"421-432"},"PeriodicalIF":2.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105125","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":"Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration.","authors":"Mohammad Tollabi, Zahra Poursalehi, Parichehr Mehrafshar, Rayhaneh Bakhtiari, Vahid Hosseinpour Sarmadi, Lobat Tayebi, Seyed Mohammad Amin Haramshahi","doi":"10.1080/03008207.2024.2396002","DOIUrl":"10.1080/03008207.2024.2396002","url":null,"abstract":"<p><p>Features of the extracellular matrix, along with biochemical factors, have a momentous impress in making genes on and/or off. The interaction of cells and the extracellular matrix is mediated by integrins. Therefore, these molecules have pivotal roles in regulating cell behaviors. Integrins include a group of molecules with a variety of characteristics that can affect different molecular cascades. Considering the importance of these molecules in tissue regeneration after injury, it is necessary to know well the integrins involved in the process of connecting cells to the extracellular matrix in each tissue.With the increase in life expectancy, bone tissue engineering has received more attention from researchers. Integrins are critical components in osteoblast differentiation, survival, and bone mechanotransduction. During osteogenic differentiation in stem cells, specific integrins facilitate multiple signaling pathways through their cytoplasmic domain, leading to the induction of osteogenic differentiation. Also, due to the importance of using biomaterials in bone tissue engineering, efforts have been made to design and use biomaterials with maximum interaction with integrins. Notably, the use of RGD peptide or fibronectin for surface modification is a well-established and commonly employed approach to manipulate integrin activity.This review article looks into integrins' role in bone development and regeneration. It then goes on to explore the complex mechanisms by which integrins contribute to these processes. In addition, this review discusses the use of natural and synthetic biomaterials that target integrins to promote bone regeneration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"343-363"},"PeriodicalIF":2.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281576","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}

{"title":"Impact of NaOH based perfusion-decellularization protocol on mechanical resistance of structural bone allografts.","authors":"Robin Evrard, Maxendre Feyens, Julie Manon, Benoit Lengelé, Olivier Cartiaux, Thomas Schubert","doi":"10.1080/03008207.2024.2356586","DOIUrl":"10.1080/03008207.2024.2356586","url":null,"abstract":"<p><strong>Introduction: </strong>To mitigate the post-operative complication rates associated with massive bone allografts, tissue engineering techniques have been employed to decellularize entire bones through perfusion with a sequence of solvents. Mechanical assessment was performed in order to compare conventional massive bone allografts and perfusion/decellularized massive bone allografts.</p><p><strong>Material and methods: </strong>Ten porcine femurs were included. Five were decellularized by perfusion. The remaining 5 were left untreated as the \"control\" group. Biomechanical testing was conducted on each bone, encompassing five different assessments: screw pull-out, 3-points bending, torsion, compression and Vickers indentation.</p><p><strong>Results: </strong>Under the experimental conditions of this study, all five destructive tested variables (maximum force until screw pull-out, maximum elongation until screw pull-out, energy to pull out the screw, fracture resistance in flexion and maximum constrain of compression) were statistically significantly superior in the control group. All seven nondestructive variables (Young's modulus in flexion, Young's modulus in shear stress, Young's modulus in compression, Elastic conventional limit in compression, lengthening to rupture in compression, resilience in compression and Vickers Hardness) showed no significant difference.</p><p><strong>Discussion: </strong>Descriptive statistical results suggest a tendency for the biomechanical characteristics of decellularized bone to decrease compared with the control group. However, statistical inferences demonstrated a slight significant superiority of the control group with destructive mechanical stresses. Nondestructive mechanical tests (within the elastic phase of Young's modulus) were not significantly different.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"279-292"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087037","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":"Biomechanical outcomes of pharmacological therapies for post-traumatic arthrofibrosis in preclinical animal models: a systematic review and meta-analysis.","authors":"Luis Palacios-Díaz, Ángel Antonio González-Garcia, Pablo Sánchez Urgellés, Samuel Antuña, Raúl Barco","doi":"10.1080/03008207.2024.2358351","DOIUrl":"10.1080/03008207.2024.2358351","url":null,"abstract":"<p><strong>Purpose/aim of the study: </strong>There is still no evidence of which drug has the greatest therapeutic potential for post-traumatic arthrofibrosis. The aim of this study is to systematically review the literature for quality evidence and perform a meta-analysis about the pharmacological therapies of post-traumatic arthrofibrosis in preclinical models.</p><p><strong>Materials and methods: </strong>A comprehensive and systematic search strategy was performed in three databases (MEDLINE, EMBASE and Web of Science) retrieving studies on the effectiveness of pharmacological therapies in the management of post-traumatic arthrofibrosis using preclinical models in terms of biomechanical outcomes. Risk of bias assessment was performed using the SYRCLE's risk of bias tool. A meta-analysis using a random-effects model was conducted if a minimum of three studies reported homogeneous outcomes for drugs with the same action mechanism.</p><p><strong>Results: </strong>Forty-six studies were included in the systematic review and evaluated for risk of bias. Drugs from 6 different action mechanisms of 21 studies were included in the meta-analysis. Overall, the methodological quality of the studies was poor. Statistically significant overall effect in favor of reducing contracture was present for anti-histamines (Chi2 <i>p</i> = 0.75, I2 = 0%; SMD (Standardized Mean Difference) = -1.30, 95%CI: -1.64 to -0.95, <i>p</i> < 0.00001) and NSAIDs (Chi2 <i>p</i> = 0.01, I2 = 63%; SMD= -0.93, 95%CI: -1.58 to -0.28, <i>p</i> = 0.005).</p><p><strong>Conclusions: </strong>Anti-histamines, particularly ketotifen, have the strongest evidence of efficacy for prevention of post-traumatic arthrofibrosis. Some studies suggest a potential role for NSAIDs, particularly celecoxib, although heterogeneity among the included studies is significant.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"265-278"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174910","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":"miR-20a: a key regulator of orthodontic tooth movement via BMP2 signaling pathway modulation.","authors":"Zhi-Hui Mai, Jin-Hua Huang, Zhu-Li Peng, Yan-Jun Pan, Zhi-Wen Sun, Hong Ai","doi":"10.1080/03008207.2024.2365201","DOIUrl":"10.1080/03008207.2024.2365201","url":null,"abstract":"<p><strong>Aim: </strong>In this study, we aimed to establish a rat tooth movement model to assess miR-20's ability in enhancing the BMP2 signaling pathway and facilitate alveolar bone remodeling.</p><p><strong>Method: </strong>60 male SD rats had nickel titanium spring devices placed between their left upper first molars and incisors, with the right side serving as the control. Forces were applied at varying durations (18h, 24h, 30h, 36h, 42h, 1d, 3d, 5d, 7d, 14d), and their bilateral maxillary molars and surrounding alveolar bones were retrieved for analysis. Fluorescent quantitative PCR was conducted to assess miR-20a, BMP2, Runx2, Bambi and Smad6 gene expression in alveolar bone, and western blot was performed to determine the protein levels of BMP2, Runx2, Bambi, and Smad6 after mechanical loading.</p><p><strong>Result: </strong>We successfully established an orthodontic tooth movement model in SD rats and revealed upregulated miR-20a expression and significantly increased BMP2 and Runx2 gene expression and protein synthesis in alveolar bone during molar tooth movement. Although Bambi and Smad6 gene expression did not significantly increase, their protein synthesis was found to decrease significantly.</p><p><strong>Conclusion: </strong>MiR-20a was found to be involved in rat tooth movement model alveolar bone remodeling, wherein it promoted remodeling by reducing Bambi and Smad6 protein synthesis through the BMP2 signaling pathway.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"304-312"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455742","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":"β-glycerophosphate, not low magnitude fluid shear stress, increases osteocytogenesis in the osteoblast-to-osteocyte cell line IDG-SW3.","authors":"Robert Owen, Claudia Wittkowske, Damien Lacroix, Cecile M Perrault, Gwendolen C Reilly","doi":"10.1080/03008207.2024.2375065","DOIUrl":"10.1080/03008207.2024.2375065","url":null,"abstract":"<p><strong>Aim: </strong>As osteoblasts deposit a mineralized collagen network, a subpopulation of these cells differentiates into osteocytes. Biochemical and mechanical stimuli, particularly fluid shear stress (FSS), are thought to regulate this, but their relative influence remains unclear. Here, we assess both biochemical and mechanical stimuli on long-term bone formation and osteocytogenesis using the osteoblast-osteocyte cell line IDG-SW3.</p><p><strong>Methods: </strong>Due to the relative novelty and uncommon culture conditions of IDG-SW3 versus other osteoblast-lineage cell lines, effects of temperature and media formulation on matrix deposition and osteocytogenesis were initially characterized. Subsequently, the relative influence of biochemical (β-glycerophosphate (βGP) and ascorbic acid 2-phosphate (AA2P)) and mechanical stimulation on osteocytogenesis was compared, with intermittent application of low magnitude FSS generated by see-saw rocker.</p><p><strong>Results: </strong>βGP and AA2P supplementation were required for mineralization and osteocytogenesis, with 33°C cultures retaining a more osteoblastic phenotype and 37°C cultures undergoing significantly higher osteocytogenesis. βGP concentration positively correlated with calcium deposition, whilst AA2P stimulated alkaline phosphatase (ALP) activity and collagen deposition. We demonstrate that increasing βGP concentration also significantly enhances osteocytogenesis as quantified by the expression of green fluorescent protein linked to Dmp1. Intermittent FSS (~0.06 Pa) rocker had no effect on osteocytogenesis and matrix deposition.</p><p><strong>Conclusions: </strong>This work demonstrates the suitability and ease with which IDG-SW3 can be utilized in osteocytogenesis studies. IDG-SW3 mineralization was only mediated through biochemical stimuli with no detectable effect of low magnitude FSS. Osteocytogenesis of IDG-SW3 primarily occurred in mineralized areas, further demonstrating the role mineralization of the bone extracellular matrix has in osteocyte differentiation.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"313-329"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562867","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}

{"title":"SRGN promotes macrophage recruitment through CCL3 in osteoarthritis.","authors":"Yi Zhang, Zihua Li, Cheng Chen, Wang Wei, Zhendong Li, Haichao Zhou, Wenbao He, Jiang Xia, Bing Li, Yunfeng Yang","doi":"10.1080/03008207.2024.2380313","DOIUrl":"10.1080/03008207.2024.2380313","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a degenerative disease that affects synovial joints and leads to significant pain and disability, particularly in older adults. Infiltration of macrophages plays a key role in the progression of OA. However, the mechanisms underlying macrophage recruitment in OA are not fully understood.</p><p><strong>Methods: </strong>The Serglycin (SRGN) expression pattern was analyzed, along with its association with macrophage infiltration in OA, using bioinformatic methods. SRGN expression in chondrocytes was altered by small interfering RNA (siRNA) and plasmids. Conditioned media (CM) was obtained from transfected chondrocytes to establish a co-culture model of chondrocytes and THP-1 derived macrophages. The impact of SRGN on macrophage recruitment was evaluated using a transwell assay. Furthermore, the regulatory effect of SRGN on CCL3 was validated through qPCR, WB, and ELISA experiments.</p><p><strong>Results: </strong>In OA patients, the upregulation of SRGN positively correlated with K-L grade and macrophage infiltration. It was found that SRGN expression and secretion were up-regulated in OA and that it can promote macrophage migration in vitro. Further investigation showed that SRGN affects macrophage migration by regulating the expression of CCL3.</p><p><strong>Conclusion: </strong>SRGN in chondrocytes plays a role in promoting the recruitment of THP-1 derived macrophages in vitro by regulating production of CCL3.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"330-342"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787515","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":"TXNIP mediated by EZH2 regulated osteogenic differentiation in hBmscs and MC3T3-E1 cells through the modulation of oxidative stress and PI3K/AKT/Nrf2 pathway.","authors":"Weibo Zhou, Chunhui Zhu, Fulin Zhou","doi":"10.1080/03008207.2024.2358361","DOIUrl":"10.1080/03008207.2024.2358361","url":null,"abstract":"<p><strong>Background: </strong>Previous research has identified a significant role of Thioredoxin-interacting protein (TXNIP) in bone loss. The purpose of this investigation was to assess the role and the underlying molecular mechanisms of TXNIP in the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) and pre-osteoblast MC3T3-E1 cells.</p><p><strong>Methods: </strong>Human bone marrow stem cells (hBMSCs) and MC3T3-E1 cells were used to induce osteogenic differentiation. The expression of genes and proteins was assessed using RT-qPCR and western blot, respectively. ChIP assay was used to validate the interaction between genes. The osteogenic differentiation ability of cells was reflected using ALP staining and detection of ALP activity. The mineralization ability of cells was assessed using ARS staining. DCFCA staining was employed to evaluate the intracellular ROS level.</p><p><strong>Results: </strong>Initially, downregulation of TXNIP and upregulation of EZH2 were observed during osteogenesis in hBMSCs and MC3T3-E1 cells. Additionally, it was discovered that EZH2 negatively regulates TXNIP expression in these cells. Furthermore, experiments indicated that the knockdown of TXNIP stimulated the activation of the PI3K/AKT/Nrf2 signaling pathway in hBMSCs and MC3T3- E1 cells, thus inhibiting the production of reactive oxygen species (ROS). Further functional experiments revealed that overexpression of TXNIP inhibited the osteogenic differentiation in hBMSCs and MC3T3-E1 cells by enhancing ROS produc-tion. On the other hand, knockdown of TXNIP promoted the osteogenic differentiation capacity of hBMSCs and MC3T3-E1 cells through the activation of the PI3K/AKT/Nrf2 pathway.</p><p><strong>Conclusion: </strong>In conclusion, this study demonstrated that TXNIP expression, under the regulation of EZH2, plays a crucial role in the osteogenic differentiation of hBMSCs and MC3T3-E1 cells by regulating ROS production and the PI3K/AKT/Nrf2 pathway.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"293-303"},"PeriodicalIF":2.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330496","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}