Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway
文献类型：期刊论文
| 作者 | Fan, Shu-Hui1,4; Chang, Yuan1,4; Xiong, Xiao-Yu1,4; Xiang, Mai1,2; Yuan, Wen-Long1,2; Yang, Xiao-Qian1; Wei, Wen-Hui1,2; Chen, Li1; Cheng, Meng-Nan1; Zhu, Feng-Hua1 |
| 刊名 | BIOMEDICINE & PHARMACOTHERAPY
 |
| 出版日期 | 2024 |
| 卷号 | 170页码:6 |
| ISSN号 | 0753-3322 |
| 关键词 | DZ2002 Osteoarthritis Osteoclast Bone resorption |
| DOI | 10.1016/j.biopha.2023.115975 |
| 通讯作者 | He, Shi-Jun(heshijun@shutcm.edu.cn) ; Zuo, Jian-Ping(jpzuo@simm.ac.cn) ; Lin, Ze-Min(linzemin@simm.ac.cn) |
| 英文摘要 | Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent lowgrade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA. The cytotoxicity of DZ2002 was evaluated using the MTT assay on bone marrow-derived macrophages. The inhibitory impact of DZ2002 during the process of osteoclastogenesis was assessed using TRAP staining, analysis of bone resorption pits, and F-actin ring formation. Mechanistic insights were derived from qPCR and Western blot analyses. Through the intra-articular injection of monosodium iodoacetate (MIA), an experimental rat model of OA was successfully instituted. This was subsequently accompanied by a series of assessments including Von Frey filament testing, analysis of weight-bearing behaviors, and micro-CT imaging, all aimed at assessing the effectiveness of DZ2002. The findings emphasized the effectiveness of DZ2002 in mitigating osteoclastogenesis induced by M-CSF/RANKL, evident through a reduction in TRAP-positive OCs and bone resorption. Moreover, DZ2002 modulated bone resorption-associated gene and protein expression (CTSK, CTR, Integrin beta 3) via the MEK/ERK pathway. Encouragingly, DZ2002 also alleviates MIA-induced pain, cartilage degradation, and bone loss. In conclusion, DZ2002 emerges as a potential therapeutic contender for OA, as evidenced by its capacity to hinder in vitro M-CSF/RANKL-induced osteoclastogenesis and mitigate in vivo osteoarthritis progression. This newfound perspective provides substantial support for considering DZ2002 as a compelling agent for osteoarthritis intervention. |
| 资助项目 | National Natural Science Foundation of China[82374108] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0120232003] ; Shanghai Municipal Science and Technology Major Project ; State Key Laboratory of Drug Research[SKLDR-2023 -KF-02] |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| WOS记录号 | WOS:001140095400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308769]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | He, Shi-Jun; Zuo, Jian-Ping; Lin, Ze-Min |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210029, Jiangsu, Peoples R China 5.Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Fan, Shu-Hui,Chang, Yuan,Xiong, Xiao-Yu,et al. Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway[J]. BIOMEDICINE & PHARMACOTHERAPY,2024,170:6. |
| APA | Fan, Shu-Hui.,Chang, Yuan.,Xiong, Xiao-Yu.,Xiang, Mai.,Yuan, Wen-Long.,...&Lin, Ze-Min.(2024).Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway.BIOMEDICINE & PHARMACOTHERAPY,170,6. |
| MLA | Fan, Shu-Hui,et al."Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway".BIOMEDICINE & PHARMACOTHERAPY 170(2024):6. |
入库方式： OAI收割
来源：上海药物研究所
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