Journal of Inflammation Research最新文献

{"title":"Extracellular Vesicles in Periodontitis: Pathogenic Mechanisms and Therapeutic Potential.","authors":"Ling Zhang, Xiaotong Li, Bin Zhang, Ruiji Li","doi":"10.2147/JIR.S504612","DOIUrl":"10.2147/JIR.S504612","url":null,"abstract":"<p><p>Periodontitis is a prevalent yet frequently overlooked oral disease that is linked to a range of systemic conditions. Although basic treatment and periodontal surgery can alleviate the symptoms of periodontitis to a certain extent, the treatment of severe tissue defects or refractory cases is not effective. Extracellular vesicles (EVs) are subcellular lipid bilayer particles that come from a variety of sources and are prevalent in the biological fluids of vertebrates. They play a key role in intercellular communication by transporting multiple signaling molecules. Recent research has indicated that EVs derived from periodontal pathogens can trigger periodontitis, exacerbate the periodontal damage, and potentially disseminate to other parts of the body, leading to systemic conditions. Conversely, extracellular vesicles derived from dental stem cells (DSCs) have demonstrated the ability to regulate the local periodontal immune environment and foster the regeneration and repair of periodontal tissues, positioning them as a promising candidate for cell-free therapeutic approaches to periodontitis. This review aims to summarize the latest research on the involvement of EVs from different sources in the pathogenesis and treatment of periodontitis, especially to systematically elucidate the mechanism of EVs secreted by periodontal pathogens in periodontitis-related systemic diseases for the first time. By uncovering these complex regulatory processes, new and more effective therapeutic approaches can be explored in the battle against periodontitis and its associated systemic diseases.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1317-1331"},"PeriodicalIF":4.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-Weighted Network Pharmacology: Evaluating Traditional Chinese Medicine Formulations for Lumbar Disc Herniation.","authors":"Changwen Zhou, Ting Xiang, Yu Yu, Hongzhong Ma, Ce Liu, Feng Yang, Lixue Yang","doi":"10.2147/JIR.S496124","DOIUrl":"10.2147/JIR.S496124","url":null,"abstract":"<p><strong>Background and purpose: </strong>Lumbar disc herniation (LDH) significantly impacts individuals, particularly those aged 40-45. Traditional Chinese Medicine (TCM) formulations such as Taohong Siwu Decoction (TSD), Yaotong Jizheng Decoction (YJD), and Panlong Qi Tablet (PQT) are widely used for treatment. This study introduces dose-weighted network pharmacology, a novel approach that incorporates drug dosage as a quantitative factor into network analysis to evaluate better and compare the therapeutic potential of TCM formulations.</p><p><strong>Methods: </strong>This study combines drug dosage with the PPI network to propose a theoretical algorithm for comparing the therapeutic efficacy of different traditional Chinese medicine formulations. The VIKOR method was used to assess the importance of therapeutic targets, with weights assigned based on both drug and disease perspectives. TSD, YJD, and PQT were evaluated in animal experiments, and the algorithm's feasibility was validated through GO and KEGG pathway analysis, Thermal Hyperalgesia Test, H&E staining, Western blotting (WB), RT-PCR, and ELISA assays.</p><p><strong>Results: </strong>The computational model indicated that YJD and PQT had higher predicted efficacy compared to TSD. These predictions were confirmed in animal studies, where YJD demonstrated the greatest reduction in thermal hyperalgesia and the most significant decrease in inflammatory markers, surpassing both TSD and PQT. GO and KEGG pathway analyses highlighted key pathways related to oxidative stress and inflammation, providing mechanistic insights into the effectiveness of the treatments.</p><p><strong>Conclusion: </strong>Incorporating dosage as a reference factor into network pharmacology research proved feasible and effective, emphasizing the importance of precise dosage control in TCM formulations for treating LDH. The new algorithm provided reliable predictions, demonstrating its potential to enhance the design and evaluation of TCM formulations. Future improvements, such as establishing a target acceptance rate database, could further refine the algorithm, expanding its application in personalized medicine and targeted therapy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1281-1300"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Predictive Value of SII and NLR in LAA Stroke: Addressing Unexplored Limitations and Future Directions [Letter].","authors":"E Zhao, Zhengting Duan, Jingmei Li","doi":"10.2147/JIR.S517359","DOIUrl":"10.2147/JIR.S517359","url":null,"abstract":"","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1301-1302"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture.","authors":"Tyler C Moore, Terrence Scott Pinkerton, Thomas M Petro","doi":"10.2147/JIR.S496930","DOIUrl":"10.2147/JIR.S496930","url":null,"abstract":"<p><strong>Introduction: </strong>Macrophage responses to lipopolysaccharides (LPS) drive inflammatory diseases, such as periodontitis, with production of IL-6 and Nitric Oxide (NO). However, anti-inflammatory macrophages counter inflammation with the production of CCL22. Interferon regulatory factor 3 (IRF3) plays a significant role in expression of both IL-6 and NO during macrophage responses through Interferon-stimulated Response Elements (ISREs) of promoters.</p><p><strong>Methods: </strong>To determine the role of IRF3 in LPS-induced pro- and anti-inflammatory macrophage responses, we used the macrophage cell line RAW264.7 modified with an ISRE promoter driving secreted luciferase (RAW264.7-Lucia) to assess IRF3 activity in response to <i>Escherichia coli</i> and <i>Porphyromonas gingivalis</i> LPS. For comparison, responses to poly I:C and IFN-gamma and responses from RAW264.7 cells deficient in IRF3 were also assessed.</p><p><strong>Results: </strong>Herein, LPS of <i>P. gingivalis</i>, significantly enhanced production of IL-6 and NO that was induced by <i>E. coli</i> LPS but significantly decreased poly I:C-induced ISRE promoter activity. Moreover, IRF3 deficiency depressed the LPS-induced ISRE promoter activity and NO production but increased IL-6 and CCL22 in response to LPS. Restoration of IRF3 expression in IRF3KO RAW cells increased IL-6, restored NO, and decreased CCL22 production in response to LPS of <i>E. coli</i>.</p><p><strong>Discussion: </strong>Therefore, IRF3 is critical to the expression of pro- and anti-inflammatory factors produced by macrophages responding to LPS and could be a target during periodontitis treatment.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1255-1265"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered CD73-Adenosine Signaling Linked to Infection in Patients undergoing hemodialysis.","authors":"Fangfang Xiang, Zhen Zhang, Yuxin Nie, Xuesen Cao, Yang Li, Xiaohong Chen, Shaomin Gong, Jianzhou Zou, Jie Teng, Xiaoqiang Ding, Bo Shen","doi":"10.2147/JIR.S498575","DOIUrl":"10.2147/JIR.S498575","url":null,"abstract":"<p><strong>Purpose: </strong>Infection is the most common cause of hospitalization and the second most common cause of mortality among patients undergoing hemodialysis (HD). The enzyme CD73, a cell surface 5'-nucleotidase, regulates the balance between pro-inflammatory nucleotides and anti-inflammatory adenosine. Diminished CD73-adenosine signaling contributes to severe infections.</p><p><strong>Methods: </strong>In this prospective cohort study, 393 patients who underwent HD for over six months were evaluated for CD73⁺Tcell ratios and were followed up for three years to track infection events. Kaplan-Meier curves and Cox regression analyses were used to evaluate the relationship between CD73⁺T cells and infections; meanwhile, multiple logistic regression analysis was used to analyze differences among infection groups. In addition, a 5/6 nephrectomy (5/6 Nx) rat model and cecal ligation and puncture (CLP) were used to verify the effect of chronic kidney disease (CKD) and sepsis on CD73-adenosine signaling.</p><p><strong>Results: </strong>Decreased CD73⁺ T cells were independently associated with increased infection risk over one and three years. The hazard ratios for one- and three-year infection incidences were 3.173 (95% CI 1.782-5.650, p < 0.001) and 1.429 (95% CI 1.052-1.992, p = 0.035), respectively. Furthermore, they were associated with recurrent and fatal severe infections. Animal models demonstrated reduced CD73 mRNA transcript and adenosine receptor levels, along with decreased serum adenosine levels in CKD. Impairment of CD73-adenosine signaling was more pronounced after CLP in CKD rats.</p><p><strong>Conclusion: </strong>Lower CD73⁺T cell levels are strongly associated with infection complications in patients undergoing HD. Altered CD73-adenosine signaling likely plays a substantial role in immune dysfunction in CKD.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1267-1279"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate Ameliorates Kainic Acid-Induced Neuroinflammation and Cognitive Impairment via the Chemokine Signaling Pathway in Mice.","authors":"Xiaoqi Chu, Yusong Ge, Chao Geng, Peipei Cao, Penghu Wei, Bin Fu, Zihao Deng, Yuhao Li, Guoguang Zhao","doi":"10.2147/JIR.S498738","DOIUrl":"10.2147/JIR.S498738","url":null,"abstract":"<p><strong>Purpose: </strong>Lactate, previously considered a metabolic waste product, has been shown to have neuroprotective potential. This study aims to investigate the impact of lactate intervention and its underlying mechanisms on epilepsy.</p><p><strong>Methods: </strong>HT22 cells were stimulated with glutamate to construct an excitotoxicity cell model. An acute epilepsy model was established in mice by kainic acid induction. The neuronal damage, microglial activation, inflammatory responses, and functional changes were determined by TUNEL assays, immunohistochemistry, quantitative real-time polymerase chain reaction and behavioral tests. The differentially gene expression and functional enrichment were analyzed with RNA sequencing.</p><p><strong>Results: </strong>The in vitro lactate intervention reduced the number of apoptotic cells, the release of inflammatory factors, and the expression of vesicular glutamate transporter 1. In mice with acute epilepsy, lactate treatment mitigated neuronal damage, microglial activation, and inflammatory responses in the hippocampus and ameliorated anxiety-like behavior and cognitive impairment.</p><p><strong>Conclusion: </strong>Lactate exerts therapeutic effects on epilepsy through the chemokine signaling pathway. The neuroinflammation is an important contributor to cognitive impairment. Targeting inflammatory pathways is a promising strategy for improving the prognosis of epilepsy.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1235-1254"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Proallergenic Activity of <i>Tranzschelia pruni-spinosae</i> and <i>Phragmidium rubi-idaei</i> in vitro Studies.","authors":"Monika Sztandera-Tymoczek, Sylwia Wdowiak-Wróbel, Urszula Świderska, Marta Palusińska-Szysz, Agnieszka Szuster-Ciesielska","doi":"10.2147/JIR.S497219","DOIUrl":"10.2147/JIR.S497219","url":null,"abstract":"<p><strong>Purpose: </strong>Allergic diseases have escalated to epidemic levels worldwide, impacting nearly 30% of the global population. Fungi are a significant source of allergens responsible for up to 6% of respiratory diseases in the general population. However, the specific cause of respiratory allergies often remains unidentified. This study aimed to investigate the potential of two common rust fungi, <i>Tranzschelia pruni-spinosae</i> and <i>Phragmidium rubi-idaei</i>, to trigger a proinflammatory response in vitro models representing the upper and lower respiratory tract.</p><p><strong>Materials and methods: </strong>The BEAS-2B and A549 cell lines simulated upper and lower respiratory endothelial cells. The cytotoxicity of fungal extracts was evaluated using MTT and flow cytometry assays. Cell reactive oxygen species (ROS) production was measured via flow cytometry, while ELISA tests quantified the production of proinflammatory cytokines. Immunofluorescence techniques were employed to assess cell integrity markers.</p><p><strong>Results: </strong>Extracts from <i>T. pruni-spinosae</i> and <i>P. rubi-idaei</i> significantly stimulated the production of proinflammatory cytokines IL-1β and GM-CSF in both cell lines, all of which are associated with the development of allergic responses. The increase in these cytokines and the elevated ROS production were linked to the disruption of epithelial cell junctions.</p><p><strong>Conclusion: </strong>The findings suggest the potential of <i>T. pruni-spinosae</i> and <i>P. rubi-idaei</i> extracts to collectively disrupt the epithelial barrier in the upper and lower respiratory tract by inducing proinflammatory cytokines and the production of reactive oxygen species and metalloproteinases. Although none of the above parameters was spectacularly high, all of them together could cause a decrease in the presence of tight junction proteins, such as E-cadherin and occludin, in epithelial cells.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1107-1125"},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11777704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Upregulation of IL-1β Induced by Cisplatin Triggers PI3K/AKT/MMP9 Pathway in Pericytes Mediating the Leakage of the Blood Labyrinth Barrier.","authors":"Miao Yu, Wen-Jun Jiang, Meng Yu, Zan Zhou, Min Wang, Li Li","doi":"10.2147/JIR.S492292","DOIUrl":"10.2147/JIR.S492292","url":null,"abstract":"<p><strong>Background: </strong>Blood-labyrinth barrier (BLB) damage has been recognized as a key mechanism underlying cisplatin (CDDP)-induced hearing loss. Inflammation within the cochlea, triggered by CDDP, is a key pathological response. However, the relationship between CDDP-induced inflammation and BLB dysfunction remains elusive.</p><p><strong>Materials and methods: </strong>In vivo and in vitro BLB models were used to explore the inflammatory mechanisms underlying CDDP ototoxicity. C57BL/6J mice were treated with CDDP and IL-1β levels, BLB permeability, and hearing thresholds were assessed using ELISA, histological staining, ABR test and BLB leakage tests. In vitro BLB models, the effect of IL-1β on MMP9 expression, PI3K-AKT pathway activation, and endothelial barrier permeability were examined via Western blot, TEER value test, and FITC extraction analysis. In addition, inhibitors of IL-1β, MMP9, and PI3K-AKT were used to analyze the specific mechanisms.</p><p><strong>Results: </strong>After CDDP treatment, IL-1β upregulation in the stria vascularis disrupted tight junctions, increased BLB permeability, and led to hearing loss. Notably, IL-1β inhibition with AS101 attenuated hearing threshold elevation and BLB damage in CDDP-treated mice. Mechanistically, CDDP triggered IL-1β release from endothelial cells. IL-1β promoted MMP9 secretion from pericytes via the PI3K/AKT pathway, leading to disruption of tight junctions. Both MMP9 and PI3K-AKT inhibitors abrogated IL-1β-induced changes.</p><p><strong>Conclusion: </strong>Our findings suggest that<b> </b>CDDP initiates a cascade of events starting with IL-1β release from endothelial cells. This release triggers the activation of PI3K/AKT pathway and upregulation of MMP9 expression in pericytes, which increases BLB permeability and leds to hearing loss. IL-1β and the PI3K-AKT pathway are promising therapeutic targets,offering hope for patients with CDDP-induced hearing loss.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1191-1205"},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-1 Receptor-Associated Kinase-3 Aggravates Neuroinflammatory Injury After Intracerebral Hemorrhage via Activation NF-κB/IL-17A Pathway in Mice.","authors":"Jun Wang, Yulong Li, Chunyu Tan, Jinlian Shao, Weitai Tang, Quan Kong, Wenqianjun Sheng, Zhiquan Ding, Feng Li, Jifeng Piao, Dingyi Lv, Libin Hu, Qinghua Wang, Xiaodan Jiang","doi":"10.2147/JIR.S494611","DOIUrl":"https://doi.org/10.2147/JIR.S494611","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammatory reactions are crucial factors in secondary brain damage following intracerebral hemorrhage (ICH). Although previous studies have shown that IRAK3 is involved in immune responses, the potential effects of IRAK3 on ICH remain unclear.</p><p><strong>Methods: </strong>Collagenase IV-induced ICH mouse model. Western blotting was used to determine the expression of IRAK3 at different time points following ICH. Immunofluorescence was used to investigate the cellular localization of IRAK3. The ICH model was treated with recombinant human IRAK3 (rh-IRAK3) or IRAK3 siRNA via an intracerebroventricular injection. The effect of IRAK3 on ICH mice was assessed by Western blotting and short-term and long-term neurological function evaluation. RNA-seq was performed to explore the mechanism by which IRAK3 promotes inflammation after ICH. The mechanisms of IRAK3 and neuroinflammation will be further investigated by Western blotting, qRT-PCR and immunofluorescence. Recombinant IL-17A was used to investigate the connection between IRAK3 and the NF-κB/IL-17A signaling pathway in vivo and in vitro experiments.</p><p><strong>Results: </strong>The expression of IRAK3 increased, peaking at 24 h, followed by a subsequent decrease after ICH. IRAK3 is mainly expressed in the microglia. RNA-seq analysis revealed 1,797 differentially expressed genes around the perihematomal brain tissue after IRAK3 siRNA treatment, with multiple inflammatory pathways being downregulated. Rh-IRAK3 treatment resulted in upregulation of the levels of inflammatory cytokines around the perihematomal tissue and exacerbated neurological function deficits. Furthermore, IRAK3 siRNA treatment markedly decreased the expression of inflammatory cytokines and microglial activation via the NF-κB/IL-17A signaling pathway. Recombinant IL-17A exacerbated the inflammatory response in vivo and in vitro; however, IRAK3 knockdown reversed this process.</p><p><strong>Conclusion: </strong>IRAK3 aggravates neuroinflammation by activating the NF-κB/IL-17A signaling pathway, thereby exacerbating neurological deficits following ICH. Therefore, inhibition IRAK3 may be a promising approach for treating ICH.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1167-1189"},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism-Related Adipokines and Metabolic Diseases: Their Role in Osteoarthritis.","authors":"Qian Zhang, Yi Xuan Zhao, Long Fei Li, Qian Qian Fan, Bin Bin Huang, Hong Zhen Du, Chen Li, Wei Li","doi":"10.2147/JIR.S499835","DOIUrl":"10.2147/JIR.S499835","url":null,"abstract":"<p><p>Osteoarthritis (OA) affects several joints but tends to be more prevalent in those that are weight-bearing, such as the knees, which are the most heavily loaded joints in the body. The incidence and disability rates of OA have continued to increase and seriously jeopardise the quality of life of middle-aged and older adults. However, OA is more than just a wear and tear disease; its aetiology is complex, and its pathogenesis is poorly understood. Metabolic syndrome (MetS) has emerged as a critical driver of OA development. This condition contributes to the formation of a distinct phenotype, termed metabolic syndrome-associated osteoarthritis (MetS-OA),which differs from other metabolically related diseases by its unique pathophysiological mechanisms and clinical presentation. As key mediators of MetS, metabolic adipokines such as leptin, lipocalin, and resistin regulate inflammation and bone metabolism through distinct or synergistic signaling pathways. Their modulation of inflammatory responses and bone remodeling processes plays a critical role in the pathogenesis and progression of OA. Due to their central role in regulating inflammation and bone remodeling, metabolic adipokines not only deepen our understanding of MetS-OA pathogenesis but also represent promising targets for novel therapeutic strategies that could slow disease progression and improve clinical outcomes in affected patients.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"18 ","pages":"1207-1233"},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}