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

• Published in: Journal of translational medicine 2022-09, Vol.20 (1), p.1-428, Article 428
• Main Authors: Na, Hyun Sik, Lee, Seon-Yeong, Lee, Dong Hwan, Woo, Jin Seok, Choi, Si-Young, Cho, Keun-Hyung, Kim, Seon Ae, Go, Eun Jeong, Lee, A Ram, Choi, Jeong-Won, Kim, Seok Jung, Cho, Mi-La
• Format: Article
• Language: English
• Subjects: Animal research; Antibodies; Arthritis; Bone resorption; Care and treatment; Cartilage; Cartilage diseases; CC chemokine receptors; CCR2 protein; Chemokine receptors; Chemokines; Computed tomography; Cytokines; Development and progression; Drug withdrawal; Drugs; E3 gene; Evaluation; Fusion protein; Gamma rays; Gene therapy; Health aspects; Inflammation; Injection; Joint diseases; Laboratory animals; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Osteoarthritis; Pain; Risk factors; Small intestine; Tomography
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-022-03515-3

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.