Current molecular pharmacology最新文献

{"title":"Targeting of Lysosomes as a Therapeutic Target in Cancer.","authors":"Biyu Liu, Chengsheng Yang, Jiayi Liu, Minzhi Peng, Junquan Mao, Sanyuan Tang, Weiguo Huang","doi":"10.2174/0118761429354659250320051057","DOIUrl":"10.2174/0118761429354659250320051057","url":null,"abstract":"<p><p>Lysosomes are important intracellular organelles involved in degradation metabolism, maintenance of homeostasis, cell survival and programmed death regulation, and play an important role in immunity. Some studies have shown that lysosomes are closely linked to tumor development. Lysosomes in tumor cells increase in size and activity to adapt to rapid proliferation. Cancer cells provide strong support for their unrestricted growth and proliferation by precisely regulating the number, composition and functional activities of lysosomes and also create favorable conditions for malignant behaviors such as survival, migration, invasion, and metastatic spread of cancer cells.\u0000Lysosomes play a central role in tumor progression, and in recent years, lysosomes have become an important target for anticancer strategies aimed at interfering with their function or modulating related signaling pathways to inhibit tumors. Current anti-cancer strategies include the following five aspects: (1) targeting tumor cell energy metabolism and lysosomes to inhibit growth; (2) inhibiting lysosomal histone proteases to block degradation metabolism; (3) destabilizing lysosomal membranes to trigger tumor cell death; (4) modulating lysosomal calcium signaling to affect tumor cell function; and (5) interfering with the mTOR signaling pathway to inhibit tumor growth and proliferation. These lysosome-targeted anticancer strategies offer broad prospects and potential for the development of novel anticancer drugs and therapies and are expected to bring more effective and safer therapeutic options for cancer patients.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429354659"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mitochondrial Targeting Drug SkQ1 Attenuates the Progression of Post- Traumatic Osteoarthritis through Suppression of Mitochondrial Oxidative Stress.","authors":"Zhen-Ya Zhi, Peng-Cheng Wang","doi":"10.2174/0118761429383749250312082958","DOIUrl":"10.2174/0118761429383749250312082958","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Post-traumatic osteoarthritis (PTOA) constitutes a distinct subtype of osteoarthritis (OA). Despite extensive research, no effective pharmacological intervention has been established to prevent or halt the progression of PTOA. Current therapeutic approaches are primarily limited to symptomatic management and pain relief. SkQ1, a novel mitochondria-targeted antioxidant, has emerged as a promising therapeutic agent due to its dual capacity to scavenge excessive intracellular reactive oxygen species (ROS) and modulate inflammatory responses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to investigate the therapeutic potential of SkQ1 in the early stages of PTOA and elucidate its underlying molecular mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Chondrocytes were cultured under varying concentrations of SkQ1 to evaluate its cytotoxicity. Additionally, an in vitro oxidative stress model was established to assess the antioxidant effects of SkQ1 across different concentration levels, from which the optimal concentration for PTOA treatment was determined. The rat PTOA model was established through medial meniscal tear (MMT) surgery, followed by intra-articular administration of SkQ1 postoperatively. The gait characteristics of rats in each group were assessed biweekly following surgery. Outcome measures were evaluated at 2 and 6 weeks postoperatively, including pathological evaluation of knee cartilage, ROS levels, markers of oxidative damage, such as malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OHdG), mitochondrial membrane potential, mitochondrial DNA copy number, and apoptosis-related cytokines.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vitro, lower concentrations of SkQ1 (500 nM) exhibited superior antioxidant efficacy while minimizing cytotoxicity. The results indicated that SkQ1 administration significantly enhanced knee joint functionality and mitigated articular cartilage degeneration in both the acute and subacute phases of PTOA by inhibiting oxidative stress pathways. In a rat model of PTOA, SkQ1 not only alleviated gait abnormalities, but also substantially reduced levels of oxidative stress biomarkers, including ROS, MDA, and 8-OHdG. Furthermore, SkQ1 effectively preserved mitochondrial membrane potential and increased mitochondrial DNA copy number. Mechanistically, SkQ1 inhibited the release of cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) and downregulated key components of the mitochondria-mediated apoptotic pathway, such as Bax, Bak, cleaved caspase-3, and cleaved caspase-9.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The findings suggested that SkQ1 exerts its therapeutic effects via multiple mechanisms, including the reduction of ROS accumulation, mitigation of oxidative damage, preservation of mitochondrial function, and inhibition of apoptotic pathways. These diverse actions position SkQ1 as a promising disease-modifying agent for PTOA treatment, potentially offering benefits that extend beyond ","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429383749"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: An Essential Role of c-Fos in Notch1-mediated Promotion of Proliferation of KSHV-Infected SH-SY5Y Cells.","authors":"Huiling Xu, Jinghong Huang, Lixia Yao, Wenyi Gu, Aynisahan Ruzi, Yufei Ding, Ying Li, Weihua Liang, Jinfang Jiang, Zemin Pan, Dongdong Cao, Naiming Zhou, Dongmei Li, Jinli Zhang","doi":"10.2174/187446721701241105144436","DOIUrl":"https://doi.org/10.2174/187446721701241105144436","url":null,"abstract":"<p><p>In the online version of the article, a change was made in the author's position. The affiliation of Dongmei Li and Jinli Zhang in the online version of the article titled \"An Essential Role of c-Fos in Notch1-mediated Promotion of Proliferation of KSHV-Infected SH-SY5Y Cells\" has been updated in \"Current Molecular Pharmacology,\" 2024; 17: e18761429264583 [1]. The original article can be found online at: https://www.eurekaselect.com/article/137219 Original: Huiling Xu1,2,#, Jinghong Huang1,#, Lixia Yao1,#, Wenyi Gu3, Aynisahan Ruzi4, Yufei Ding5, Ying Li6, Weihua Liang1, Jinfang Jiang1, Zemin Pan1, Dongdong Cao1, Naiming Zhou6,7,*, Dongmei Li1,# and Jinli Zhang1,# * Address correspondence to this author at the Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, China; Tel: 86-13588743854; E-mail: zhounaiming@zju.edu.cn #This author has contributed equally to this work Corrected: Huiling Xu1,2,#, Jinghong Huang1,#, Lixia Yao1,#, Wenyi Gu3, Aynisahan Ruzi4, Yufei Ding5, Ying Li6, Weihua Liang1, Jinfang Jiang1, Zemin Pan1, Dongdong Cao1, Naiming Zhou6,7,*, Dongmei Li1,#,* and Jinli Zhang1,#,* * Address correspondence to these authors at the Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, China. Department of Biochemistry and Molecular Biology/Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine 59 North 2nd Road, Shihezi, Xinjiang, 832002 China. Department of Biochemistry and Molecular Biology/Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine 59 North 2nd Road, Shihezi, Xinjiang, 832002 China. Tel: +86-13588743854; E-mail: zhounaiming@zju.edu.cn Tel: +86-993-2057882; E-mail: lidong_abc@126.com, lidongmei@shzu.edu.cn Tel: +86-993-2057882; E-mail: jinli1998@126.com #These authors have contributed equally to this work.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e051124236081"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review.","authors":"Baljinder Singh, Charan Singh","doi":"10.2174/187446721701240911110426","DOIUrl":"https://doi.org/10.2174/187446721701240911110426","url":null,"abstract":"<p><p>In the online version of the article, a change was made in the list of author's and affiliation section. The affiliation of Charan Singh in the online version of the article titled \"Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review\" has been updated in \"Current Molecular Pharmacology,\" 2023; 16: e210422203904 [1]. The original article can be found online at: https://www.eurekaselect.com/article/122759 Original: Baljinder Singh1 1Department of Pharmaceutics, UIPS, Panjab University, Chandigarh 160014, India Corrected: 1Department of Pharmaceutics, UIPS, Punjab University, Chandigarh 160014, India 2Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India 3Department of Pharmaceutical Sciences, School of Sciences, Hemvati Nandan Bahuguna Garhwal University (A Central University), Srinagar, Uttarakhand, 246174, India Funding: Original: None. Corrected: The financial support provided by the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India, under the Research Grant File No. EEQ/2020/000616.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 ","pages":"e110924233920"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIPK1/RIPK3/MLKL Necrosome Contributes to the Sepsis-Induced Cardiorenal Necroptotic Inflammatory Injury and Mortality.","authors":"Bahar Tunctan, Muhammed Ahmed-Reda Elosman, Sefika Pinar Senol, Elif Ikiz, Tuba Kara","doi":"10.2174/0118761429374574250415114715","DOIUrl":"10.2174/0118761429374574250415114715","url":null,"abstract":"<p><strong>Introduction: </strong>Due to its critical role in inflammation and necroptotic cell death, RIPK1 has been considered a prominent therapeutic drug target for managing a wide variety of diseases, including sepsis. Therefore, we aimed to investigate whether the RIPK1-driven necroptotic pathway contributes to the nitrosative stress-mediated cardiorenal inflammatory necroptotic injury and mortality using RIPK1 inhibitor, Nec-1s, in the murine sepsis model induced by LPS.</p><p><strong>Methods: </strong>Experiments were performed using mice injected intraperitoneally with DMSO or Nec-1s with saline and/or LPS. Following euthanasia and 6 hours after the injection of these agents, arteriovenous blood samples, hearts, and kidneys of the animals were collected. Serum MPO, iNOS, CKMB, creatinine, and HMGB1 levels were measured by ELISA. Associated proteins were measured by immunoblotting. H&E staining was used to evaluate histopathological changes in the tissues. In the mortality studies, the mice were monitored every 6 hours for mortality up to 96 hours after saline, LPS, DMSO, and/or Nec-1s injection.</p><p><strong>Results: </strong>In the LPS-injected mice, a rise in serum MPO, iNOS, CK-MB, creatinine, and HMGB1 levels was associated with the enhanced expression/activity of RIPK1/RIPK3/MLKL necrosome, HMGB1, iNOS, nitrotyrosine, gp91^phox, and p47^phox, in addition to scores related to histopathological changes in their tissues. Nec-1s attenuated the LPS-induced changes. Mortality rates of 10%, 50%, and 60% were observed at the 24^th, 36^th, and 48^th hours, respectively, in the LPS-treated mice. When endotoxemic mice were treated with Nec-1s, mortality rates were 60%, 90%, and 100% at 18, 30, and 42 hours, respectively.</p><p><strong>Conclusion: </strong>These findings suggest that RIPK1/RIPK3/MLKL necrosome contributes to not only LPS-induced nitrosative stress-mediated cardiorenal inflammatory necroptotic injury, but also mortality.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429374574"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions","authors":"Rozita Khodashahi, Mahmoud Tavakkoli, Gorgon A Ferns, Leyla Feyzmohammadi, Amir Hossein Mirzaei, Mohsen Aliakbarian, Mohammad-Hassan Arjmand","doi":"10.2174/0118761429308567240806111848","DOIUrl":"10.2174/0118761429308567240806111848","url":null,"abstract":"<p><p>Post-surgical adhesion is a medical challenge, especially following abdominal and pelvic surgeries. This refers to the formation of fibrotic scars that form from connective tissue in the gynecological tract or abdominal cavity. Dysfunctional adipose tissue (AT) by surgical injuries and hypoxia increases the risk of post-surgical adhesion through different molecular mechanisms. Damage-associated molecular patterns (DAMPs) and Hypoxia-induced factor 1 alpha (HIF-1α) produced during surgery trauma and hypoxia induce AT dysfunction to promote inflammation, oxidative stress, metabolic alterations, and profibrotic pathways, which contribute to post-surgical adhesions. HIF-1α and DAMPs can be considered therapeutic targets to prevent AT dysfunction and diminish the formation of adhesions in obese patients undergoing abdominal or pelvic surgeries.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429308567"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass Spectrometry in Covalent Drug Discovery.","authors":"Chang Liu, Xiujuan Wen","doi":"10.2174/0118761429319065240605104628","DOIUrl":"https://doi.org/10.2174/0118761429319065240605104628","url":null,"abstract":"","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429319065"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloe-Emodin Relieves Myocardial Intracellular Calcium Homeostasis Imbalance Induced by High-Fat Diet <i>via</i> Protein Arginine Methyltransferase/ Ca²⁺/Calmodulin- Dependent Protein Kinase II Signaling Pathway in Rats.","authors":"Wen Li, Juan Hu, Ye Yuan, Zhimin Du, Jia Wang, Yilian Yang, Bing Shao, Jiapan Wang, Mingxiu Zhang, Chunlei Duan, Zhen Chen, Wenjie Liao, Xueqi He","doi":"10.2174/0118761429364907250319054353","DOIUrl":"10.2174/0118761429364907250319054353","url":null,"abstract":"<p><strong>Background: </strong>Chronic high-fat diets (HFDs) lead to an imbalance of calcium homeostasis in cardiomyocytes, which contributes to the development of myocardial ischemia-reperfusion injury, dilated cardiomyopathy, and other cardiovascular diseases. Aloe-emodin (AE) is an anthraquinone component isolated from aloe, rhubarb, and cassia seed, having cardiovascular protective, hepatoprotective, anti-inflammatory, and other pharmacological effects.</p><p><strong>Objective: </strong>This study aimed to explore the specific role of AE in obesity/hyperlipidemia-induced myocardial intracellular calcium homeostasis imbalance.</p><p><strong>Methods: </strong>Wistar rats (male, 220 ± 20 g) were fed HFD for four weeks and AE (100 mg/kg) was administrated for six weeks after confirmation of the HFD model. Serum lipids, reactive oxygen species levels, malondialdehyde levels, and superoxide dismutase levels were measured by commercial biochemical kits. Electrocardiograms of rats were recorded with the BL-420F biological function experimental system. Calcium transients and resting intracellular Ca2+ concentrations were determined by the Langendorff-perfused heart model. Protein levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein arginine methyltransferase 1 (PRMT1), and cardiac Ca2+ handling proteins were evaluated by western blot analysis.</p><p><strong>Results: </strong>HFD-induced hearts exhibited a reduced amplitude of Ca2+ transients and increased resting levels of [Ca2+] in the heart; AE treatment significantly improved these parameters. Furthermore, the HFD-induced heart showed downregulation of PRMT1, upregulation of CaMKII, and abnormalities in the levels of Ca2+ handling proteins. All these deleterious changes were significantly suppressed by the AE treatment. Moreover, AE treatment prevented palmitic acid (PA)-induced calcium overload in H9C2 cells; this effect was reduced by the application of an inhibitor of PRMT1.</p><p><strong>Conclusion: </strong>Taken together, this study demonstrates that AE could alleviate HFD/PA-induced myocardial intracellular calcium homeostasis imbalance via the PRMT1/CaMKII signaling pathway.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429364907"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-surgical Adhesion","authors":"Alireza Moslem, Rozita Khodashahi, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand","doi":"10.2174/0118761429302171240621101944","DOIUrl":"10.2174/0118761429302171240621101944","url":null,"abstract":"<p><p>Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts are the main mechanism that promotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. As well as, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":"e18761429302171"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repair Effect of siRNA Double Silencing of the Novel Mechanically Sensitive Ion Channels Piezo1 and TRPV4 on an Osteoarthritis Rat Model.","authors":"Zhuqing Jia, Jibin Wang, Xiaofei Li, Qining Yang, Jianguo Han","doi":"10.2174/0118761429317745241017114020","DOIUrl":"10.2174/0118761429317745241017114020","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the repair effect of siRNA-mediated double silencing of the mechanically sensitive ion channels Piezo1 and TRPV4 proteins on a rat model of osteoarthritis.</p><p><strong>Methods: </strong>Piezo1 and TRPV4 interference plasmids were constructed using siRNA technology. Sprague Dawley (SD) rats were divided into four groups: the model group, siRNA-Piezo1, siRNA-TRPV4, and double gene silencing groups. Improved Mankin and OARSI scores were calculated based on H&E staining and Safranin O-fast green staining. Immunohistochemical staining was used to determine expression levels of aggrecan and Collagen II proteins. Piezo1, TRPV4, Aggrecan, and Collagen II mRNA expression in knee joint cartilage tissue were assessed using qRT-PCR.</p><p><strong>Results: </strong>Lentivirus-mediated siRNA plasmids (siRNA-Piezo1, siRNA-TRPV4, and double-gene siRNA silencing plasmids) achieved > 90% transfection efficiency in chondrocytes. RT-PCR results indicated that double-gene siRNA silencing plasmids silenced Piezo1 and TRPV4 mRNA expression (P < 0.05). Modified Mankin and OARSI scores revealed that the repair effect in the double gene silencing group was significantly better than that of the siRNA-Piezo1 and siRNA-TRPV4 groups (P < 0.05). Relative expression of aggrecan and collagen II mRNA in the double gene-silenced group was significantly higher than in the siRNA-Piezo1 and siRNA-TRPV4 groups (P < 0.05).</p><p><strong>Conclusion: </strong>Double silencing Piezo1 and TRPV4 plays a key role in cartilage repair in an osteoarthritic rat model by promoting the expression of Aggrecan and Collagen II.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":"17 1","pages":"e18761429317745"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}