PMID- 36138477 OWN - NLM STAT- MEDLINE DCOM- 20220926 LR - 20221002 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 20 IP - 1 DP - 2022 Sep 23 TI - Soluble CCR2 gene therapy controls joint inflammation, cartilage damage, and the progression of osteoarthritis by targeting MCP-1 in a monosodium iodoacetate (MIA)-induced OA rat model. PG - 428 LID - 10.1186/s12967-022-03515-3 [doi] LID - 428 AB - BACKGROUND: Osteoarthritis (OA) is the most common type of degenerative arthritis and affects the entire joint, causing pain, joint inflammation, and cartilage damage. Various risk factors are implicated in causing OA, and in recent years, a lot of research and interest have been directed toward chronic low-grade inflammation in OA. Monocyte chemoattractant protein-1 (MCP-1; also called CCL2) acts through C-C chemokine receptor type 2 (CCR2) in monocytes and is a chemotactic factor of monocytes that plays an important role in the initiation of inflammation. The targeting of CCL2-CCR2 is being studied as part of various topics including the treatment of OA. METHODS: In this study, we evaluated the potential therapeutic effects the sCCR2 E3 gene may exert on OA. The effects of sCCR2 E3 were investigated in animal experiments consisting of intra-articular injection of sCCR2 E3 in a monosodium iodoacetate (MIA)-induced OA rat model. The effects after intra-articular injection of sCCR2 E3 (fusion protein encoding 20 amino acids of the E3 domain of the CCL2 receptor) in a monosodium iodoacetate-induced OA rat model were compared to those in rats treated with empty vector (mock treatment) and full-length sCCR2. RESULTS: Pain improved with expression of the sCCR2 gene. Improved bone resorption upon sCCR2 E3 gene activation was confirmed via bone analyses using micro-computed tomography. Histologic analyses showed that the sCCR2 E3 gene exerted protective effects against cartilage damage and anti-inflammatory effects on joints and the intestine. CONCLUSIONS: These results show that sCCR2 E3 therapy is effective in reducing pain severity, inhibiting cartilage destruction, and suppressing intestinal damage and inflammation. Thus, sCCR2 E3 may be a potential therapy for OA. CI - (c) 2022. The Author(s). FAU - Na, Hyun Sik AU - Na HS AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. AD - Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. FAU - Lee, Seon-Yeong AU - Lee SY AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. FAU - Lee, Dong Hwan AU - Lee DH AD - Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea. FAU - Woo, Jin Seok AU - Woo JS AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. FAU - Choi, Si-Young AU - Choi SY AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. FAU - Cho, Keun-Hyung AU - Cho KH AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. AD - Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. FAU - Kim, Seon Ae AU - Kim SA AD - Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea. FAU - Go, Eun Jeong AU - Go EJ AD - Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea. FAU - Lee, A Ram AU - Lee AR AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. AD - Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. FAU - Choi, Jeong-Won AU - Choi JW AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. FAU - Kim, Seok Jung AU - Kim SJ AD - Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea. peter@catholic.ac.kr. FAU - Cho, Mi-La AU - Cho ML AUID- ORCID: 0000-0001-5715-3989 AD - Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. iammila@catholic.ac.kr. AD - Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. iammila@catholic.ac.kr. AD - Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. iammila@catholic.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220923 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (Amino Acids) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Ccr2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - WF5188V710 (Iodoacetic Acid) SB - IM MH - Amino Acids/metabolism MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - Cartilage/pathology MH - *Cartilage, Articular/pathology MH - Chemokine CCL2/genetics/metabolism MH - Disease Models, Animal MH - Genetic Therapy MH - Inflammation/metabolism MH - Iodoacetic Acid/metabolism/toxicity MH - *Osteoarthritis/diagnostic imaging/genetics/therapy MH - Pain/pathology MH - Rats MH - Receptors, CCR2/genetics/metabolism MH - Receptors, Chemokine/metabolism MH - X-Ray Microtomography PMC - PMC9503236 COIS- The authors have no competing financial interests. EDAT- 2022/09/23 06:00 MHDA- 2022/09/28 06:00 PMCR- 2022/09/23 CRDT- 2022/09/22 23:46 PHST- 2021/09/07 00:00 [received] PHST- 2022/06/30 00:00 [accepted] PHST- 2022/09/22 23:46 [entrez] PHST- 2022/09/23 06:00 [pubmed] PHST- 2022/09/28 06:00 [medline] PHST- 2022/09/23 00:00 [pmc-release] AID - 10.1186/s12967-022-03515-3 [pii] AID - 3515 [pii] AID - 10.1186/s12967-022-03515-3 [doi] PST - epublish SO - J Transl Med. 2022 Sep 23;20(1):428. doi: 10.1186/s12967-022-03515-3.