MedComm最新文献

{"title":"Meal-Induced NF-kB Activation in Mononuclear Cells Triggers Lumican Secretion and Promotes Chronic Kidney Disease in Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Giovanni Musso, Filippo Mariano, Alberto Mella, Silvia Pinach, Roberto Gambino","doi":"10.1002/mco2.70122","DOIUrl":"10.1002/mco2.70122","url":null,"abstract":"","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":"e70122"},"PeriodicalIF":10.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12331869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of Chronic Pain and Therapeutic Interventions.","authors":"Zhen Li, Xing Li, Jieqiong Liu, Rao Sun, Yingze Ye, Hongbing Xiang, Fang Luo, Shiyong Li, Ailin Luo","doi":"10.1002/mco2.70325","DOIUrl":"10.1002/mco2.70325","url":null,"abstract":"<p><p>Chronic pain imposes incalculable health and economic burdens, affecting more than 30% of the global population in published studies. Optimal management of chronic pain is imperative for individuals experiencing such distress. Nevertheless, the current approaches to chronic pain assessment and treatment fail to meet clinical requirements. In recent years, there has been a growing recognition of the need for precision medicine approaches to effectively manage chronic pain. Chronic pain can be classified into three categories: nociceptive (resulting from tissue injury), neuropathic (caused by nerve injury), or nociplastic (arising from a sensitized nervous system). These classifications significantly impact the evaluation and treatment decisions at all levels. Significantly, in practice, there is substantial overlap in chronic pain mechanisms among patients and within different types of chronic pain. The application of precision medicine is imperative in the management of chronic pain. This review offers a comprehensive overview of the distinctive molecular mechanisms underlying nociceptive, neuropathic, and nociplastic pain, including immune responses, ion channels, monoaminergic imbalance, and neuroinflammation. Subsequently, we summarized the status quo of nociceptive, neuropathic, and nociplastic pain manipulation. Last, we explored the advances in pain management strategies for chronic pain that are making significant progress toward their clinical implementation.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":"e70325"},"PeriodicalIF":10.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12331885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Promising Breakthrough for Triple-Negative Breast Cancer by Targeting the AKT and EZH2","authors":"Zhuoyun Liu,&nbsp;Yirong Li,&nbsp;Xinghua Long","doi":"10.1002/mco2.70318","DOIUrl":"https://doi.org/10.1002/mco2.70318","url":null,"abstract":"&lt;p&gt;In a recent study published in &lt;i&gt;Nature&lt;/i&gt;, Cichowski et al. [&lt;span&gt;1&lt;/span&gt;] first revealed the effectiveness and potential mechanisms of combining AKT and EZH2 inhibitors (AKTi and EZH2i) for treating triple-negative breast cancer (TNBC). The study elucidated how AKTi and EZH2i work synergistically to differentiate basal-like TNBC cells into a more luminal state and hijack signaling pathways during normal breast degeneration to drive apoptosis in cancer cells, providing a new strategy for TNBC therapy.&lt;/p&gt;&lt;p&gt;The phosphoinositide 3-kinase (PI3K)/AKT1 pathway, frequently hyperactive in breast cancer, is typically activated by PIK3CA mutations in hormone receptor (HR)-positive luminal types. In contrast, phosphatase and tensin homolog (PTEN) loss predominantly drives the basal-like TNBC subtype. Existing research indicates that while PI3Kα inhibitors benefit HR-positive cancers, AKT inhibitors have shown limited efficacy in TNBC [&lt;span&gt;2&lt;/span&gt;]. In the natural involution of the mammary gland, AKT promotes the restructuring and regression of breast tissue through the regulation of apoptosis. EZH2 is instrumental in maintaining the specific states of breast cells, thereby aiding their correct signaling responses during involution [&lt;span&gt;3&lt;/span&gt;]. Cichowski's team hypothesizes that AKT inhibitors could render TNBC cells sensitive by promoting a luminal-like phenotype. EZH2 is often overexpressed in breast cancer and plays an important role in maintaining the luminal progenitor state and limiting the differentiation of luminal cells in normal mammary epithelium of mice, thus being concerned by Cichowski et al.&lt;/p&gt;&lt;p&gt;In cell tests, the AKTi was added after TNBC cell lines had been pretreated for 5 days with the EZH2i. The results showed that 60% of the cell lines were susceptible to this combination treatment, significantly reducing cell numbers within 4 days. The AKT and EZH2 inhibitors displayed negligible cytotoxic effects when taken separately but showed strong and long-lasting cytotoxic effects when taken together. Similar efficacy has been observed in multiple animal models, especially in patient-derived xenograft (PDX) models, where significant tumor regression was only triggered when the drugs were combined. The findings underscore the therapeutic potential of this inhibitor pairing in TNBC, offering a promising treatment strategy. Furthermore, the minimal weight changes observed in mouse models posttreatment affirm the combination's favorable safety and tolerability profile.&lt;/p&gt;&lt;p&gt;The study leveraged RNA sequencing to delve into the impact of the EZH2/AKTi combination on TNBC cells, uncovering substantial alterations in gene expression posttreatment. Specifically, there was an upregulation of luminal-associated genes such as GATA3 and ELF3, alongside a downregulation of basal and stem cell markers including KRT5, KRT14, and VIM. Complementary cyclic immunofluorescence imaging of HCI-004 PDX tumors validated the in vivo transition of bas","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Epigenetics in Cancer: Current Knowledge and Therapeutic Implications","authors":"Shanhe Huang,&nbsp;Zonglin Li,&nbsp;Weilong Lin,&nbsp;Ruihui Xie,&nbsp;Hai Huang","doi":"10.1002/mco2.70322","DOIUrl":"https://doi.org/10.1002/mco2.70322","url":null,"abstract":"<p>RNA epigenetics, also referred to as epitranscriptomics, has emerged as a critical regulatory layer in cancer biology, extending beyond the scope of traditional DNA and histone modifications. It encompasses a series of dynamic posttranscriptional processes—including RNA biosynthesis, splicing, transport, stability, degradation, translation, and chemical modifications—orchestrated by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs). Collectively, these mechanisms influence mRNA fate, shape transcriptional output, and reprogram the tumor microenvironment. Importantly, both coding RNA and ncRNA are themselves subjected to epigenetic regulation, forming intricate feedback loops that contribute to oncogenesis, immune evasion, metastasis, and therapeutic resistance. In this review, we systematically synthesize the current understanding of RNA metabolism and RNA epigenetic modifications during tumor progression, with a particular focus on the roles of RBPs and RNA modifications. Furthermore, we highlight recent advances in RNA-based therapeutic strategies, including mRNA vaccines, antisense oligonucleotides, siRNAs, and circRNA scaffolds. These innovative approaches offer promising avenues for targeting transcriptionally active yet genomically “undruggable” cancer drivers. Together, our synthesis provides a comprehensive framework for understanding RNA epigenetics in tumor biology and lays the groundwork for precision oncology guided by transcriptome plasticity.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-Delivered siRNA Targeting NSUN4 Relieves Systemic Lupus Erythematosus through Declining Mitophagy-Mediated CD8+T Cell Exhaustion","authors":"Bincheng Ren,&nbsp;Kaini He,&nbsp;Ning Wei,&nbsp;Shanshan Liu,&nbsp;Xiaoguang Cui,&nbsp;Xin Yang,&nbsp;Xiaojing Cheng,&nbsp;Tian Tian,&nbsp;Ru Gu,&nbsp;Xueyi Li","doi":"10.1002/mco2.70311","DOIUrl":"https://doi.org/10.1002/mco2.70311","url":null,"abstract":"<p>5-Methylcytosine modification (m5C) is an important posttranscriptional regulatory mechanism of gene expression. Exhausted CD8+T cells contribute to the development of many major diseases; however, their exact role and relationship to m5C in systemic lupus erythematosus (SLE) remain unknown. In this study, we identified a CD7^highCD74^high CD8+T subgroup that were robustly expanded in SLE patients through single-cell transcriptome sequencing (scRNA-seq). CD7^highCD74^high CD8+T cells displayed exhausted features and exhibited a superior diagnostic value in SLE. Then, we explored the m5C landscape of SLE patients by performing m5C epitranscriptome sequencing (m5C-seq). ScRNA-seq and m5C-seq were conjointly analyzed to screen m5C-related therapeutic targets for SLE, and NOP2/Sun RNA methyltransferase 4 (NSUN4) was identified as a key regulator of SLE pathogenesis. Knockdown of NSUN4 downregulated CD74 expression via reduction of m5C and suppressed CD8+T cell exhaustion by declining CD44/mTOR (mechanistic target of rapamycin kinase)-mediated mitophagy. Finally, we verified that nanoparticle-delivered siRNA against <i>Nusn4</i> decreased autoimmune reaction kidney damage in both spontaneous and pristane-induced SLE mouse models. In conclusion, we identify an exhausted CD7^highCD74^high CD8+T cell subset and propose the crucial role of NSUN4/CD74-induced dysregulation of mitophagy in SLE pathogenesis, and targeting NSUN4 is a promising treatment strategy for SLE patients.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Biological Characteristics and Mouse Model of Lassa Virus From the First Imported Case in China","authors":"Yanan Zhou,&nbsp;Junbin Wang,&nbsp;Ranran Cao,&nbsp;Yun Yang,&nbsp;Yuliang Feng,&nbsp;Cong Tang,&nbsp;Hao Yang,&nbsp;Qing Huang,&nbsp;Wenhai Yu,&nbsp;Haixuan Wang,&nbsp;Jiandong Shi,&nbsp;Kaiyun Ding,&nbsp;Longhai Yuan,&nbsp;Qing Dai,&nbsp;Xingping Zhao,&nbsp;Haiyan Li,&nbsp;Mengli Yang,&nbsp;Fangyu Luo,&nbsp;Fanli Zhu,&nbsp;Yong Zhang,&nbsp;Daoju Wu,&nbsp;Xiaorong Yang,&nbsp;Shuaiyao Lu,&nbsp;Qiangming Sun,&nbsp;Li Zhang,&nbsp;Youchun Wang","doi":"10.1002/mco2.70315","DOIUrl":"https://doi.org/10.1002/mco2.70315","url":null,"abstract":"<p>Lassa fever (LF) is a fatal hemorrhagic disease caused by the Lassa virus (LASV), which mainly spreads in Africa. As China's interactions with Africa become more frequent, the risk of LF being imported into China also rises, making the study of LASV increasingly urgent. In this study, the Lineage IV LASV strain was successfully isolated from the first imported case in China. Compared with the LASV genome, the isolated strain may exhibit greater infectivity and interspecies transmission capabilities. We successfully established BALB/c, C57BL/6, and AG129 mouse infection models and found that intranasal inoculation was the most stable infection method. Select the anti-LASV drug LHF-535 for preliminary evaluation, further confirming the stability of the model. In summary, the isolated strain exhibits enhanced transmission capabilities and may spread between mice via the respiratory tract, meriting greater attention and emphasis. This study will bridge the gap in China's independent P4-level pathogen isolation, meet national biosafety and strategic needs, and provide certain support for LASV research.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plumbagin Triggers Cuproptosis in Hepatocellular Carcinoma (HCC) via the DNA-Methyltransferase 1 (DNMT1)/microRNA-302a-3p (miR-302a-3p)/ATPase Copper Transporting Beta (ATP7B) Axis","authors":"Chuyu Wang,&nbsp;Hao Wang,&nbsp;Chong Wang,&nbsp;Tongtong Tian,&nbsp;Anli Jin,&nbsp;Yu Liu,&nbsp;Ran Huo,&nbsp;Te Liu,&nbsp;Baishen Pan,&nbsp;Wei Guo,&nbsp;Wenjing Yang,&nbsp;Beili Wang","doi":"10.1002/mco2.70312","DOIUrl":"https://doi.org/10.1002/mco2.70312","url":null,"abstract":"<p>Induction of cuproptosis in tumor cells is an emerging direction for cancer drug development. Plumbagin (PLB), a natural biological molecule, has anticancer activities, partially via copper-dependent mechanisms. But it remains unclear if PLB can induce cuproptosis in hepatocellular carcinoma (HCC). In this study, PLB showed HCC-suppressive activities and caused representative molecular phenotypes of cuproptosis, whereas tetrathiomolybdate, an inhibitor of cuproptosis, could alleviate these effects the most. The mRNA and protein expression levels of the primary hepatic copper exporter, ATPase copper transporting beta (ATP7B), decreased in PLB-treated HCC cells, which might cause the accumulation of intracellular copper and trigger cuproptosis. An upstream ATP7B-regulatory microRNA, microRNA-302a-3p (miR-302a-3p), was identified by quantification and validated by the overexpression/inhibition experiment and luciferase reporter assay. Moreover, PLB was found to reduce the protein level of DNA-methyltransferase 1 (DNMT1), thereby enhancing the promoter hypomethylation and the expression of miR-302a-3p. Gene manipulation experiments further demonstrated that ATP7B, miR-302a-3p, and DNMT1 mediated PLB-induced cuproptosis. Preliminary clinical analyses showed that low ATP7B expression levels were associated with better prognosis, supporting the importance of ATP7B-lowering therapeutic strategies in HCC. Together, our results indicate that PLB triggers HCC cuproptosis via the DNMT1/miR-302a-3p/ATP7B axis, providing a potential therapeutic strategy for HCC.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144767345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Control of AIDS Progression by an Adenovirus-Based Therapeutic Vaccination in Acute Simian Immunodeficiency Virus-Infected Macaques","authors":"Yizi He,&nbsp;Chunxiu Wu,&nbsp;Fengling Feng,&nbsp;Zijian Liu,&nbsp;Xugang Zhang,&nbsp;Qing Yang,&nbsp;Zhe Chen,&nbsp;Minjuan Shi,&nbsp;Ziyu Wen,&nbsp;Yichu Liu,&nbsp;Fengyu Hu,&nbsp;Linghua Li,&nbsp;Caijun Sun,&nbsp;Ling Chen,&nbsp;Pingchao Li","doi":"10.1002/mco2.70309","DOIUrl":"https://doi.org/10.1002/mco2.70309","url":null,"abstract":"<p>Therapeutic vaccinations that enhance human immunodeficiency virus (HIV)-specific immunity hold promise for reducing reliance on antiretroviral therapy (ART). We previously developed an adenovirus vector-infected peripheral blood mononuclear cell (AVIP) as a prophylactic strategy that enhanced cellular immunity in macaques and significantly reduced set-point and peak simian immunodeficiency virus (SIV) loads following SIV challenge. However, its therapeutic efficacy remains to be fully explored. In this study, we improved AVIP by enhancing adenovirus entry into peripheral blood mononuclear cells (PBMCs) through in vitro co-incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF). We constructed adenoviruses carrying SIV group-specific antigen (Gag), envelope (Env), and polymerase (Pol) and evaluated the therapeutic potential of autologous AVIP infusion in acute SIV-infected macaques. Compared with ART alone, AVIP in combination with ART elicited robust cellular immunity against SIV, effectively controlled SIV replication during ART, and delayed viral rebound and acquired immunodeficiency syndrome (AIDS) progression after ART discontinuation. Notably, 80% of macaques in AVIP+ART group maintain plasma virus control for at least 100 days after ART interruption. This sustained viral control is associated with vaccine-induced Pol-specific immune responses and reduced CD38 expression on CD8⁺ T cells. These findings support further investigation of AVIP as a therapeutic strategy against acute HIV infection.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T Cell-Specific Deficiency of Src Homology 2-Containing Protein Tyrosine Phosphatase 2 Ameliorates Psoriasis and Colitis by Promoting Treg Differentiation","authors":"Shuqiong Zhang,&nbsp;Zijun Ouyang,&nbsp;Zhidan Fan,&nbsp;Haiyan Sun,&nbsp;Haiguo Yu,&nbsp;Xingxin Wu,&nbsp;Yang Sun,&nbsp;Fenli Shao","doi":"10.1002/mco2.70310","DOIUrl":"https://doi.org/10.1002/mco2.70310","url":null,"abstract":"<p>Psoriasis and ulcerative colitis are both autoimmune diseases with complex pathogenesis characterized by immune disorders. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase that acts as a key regulator of immune cell-mediated inflammation. Although studies have described the role of SHP2 in autoimmune diseases, its influence on the development of regulatory T cells (Tregs) was undefined, which plays a critical role in immune homeostasis. Here, we found that imiquimod (IMQ)-induced psoriasis symptoms were milder in <i>Lck</i>-Cre;SHP2^f/f mice than those in SHP2^f/f mice, including reduced inflammatory cell infiltration and keratinocyte proliferation. The reduced Th17/Treg ratio in psoriasis models in <i>Lck</i>-Cre;SHP2^f/f mice suggests that SHP2 regulates the balance of Th17/Treg. In vitro, the deficiency of SHP2 promotes the differentiation of T cells into Tregs. In the model of adoptive transfer colitis, the SHP2-deficient CD4⁺CD25⁻CD45RB^high T cells differentiated into a greater number of Tregs within the recipient mice, resulting in attenuated symptoms of colitis. Moreover, cotransfer experiments confirmed that the deficiency of SHP2 does not affect the immunosuppressive function of Tregs. These findings establish that SHP2 reduces Treg differentiation and further confirm that SHP2 inhibitors could be utilized in the treatment of autoimmune diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoarthritis: Mechanisms and Therapeutic Advances","authors":"Wei Liu,&nbsp;Ning-Yi Guo,&nbsp;Jian-Quan Wang,&nbsp;Bing-Bing Xu","doi":"10.1002/mco2.70290","DOIUrl":"https://doi.org/10.1002/mco2.70290","url":null,"abstract":"<p>Osteoarthritis (OA) is a chronic joint disease characterized by a complex pathological mechanism, including chondrocyte dysfunction, synovial inflammation, subchondral bone remodeling, and molecular regulation abnormalities. Key signaling pathways such as nuclear factor-κB, mitoase-activated protein kinase, and transforming growth factor-β are disrupted, leading to cytokine imbalance, oxidative stress, and excessive protease activity, which collectively contribute to cartilage degeneration. This review summarizes the potential causes of OA, focusing on cellular and structural abnormalities in cartilage, synovial tissue, and subchondral bone, as well as dysregulation of signaling pathways, gene regulation, and molecular mechanisms. Given the limitations of current diagnostic methods for OA, biomarkers may offer new hope. Emerging therapeutic strategies for OA include biologics, intelligent drug delivery, and tissue engineering, aiming to modulate the immune microenvironment while promoting cartilage repair. However, these approaches face challenges such as long-term safety and scalability. Future research may require deeper multidisciplinary collaboration and combination therapies to revolutionize the management of OA and improve patient outcomes.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 8","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}