{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:30:56Z","timestamp":1787027456086,"version":"build-2736575974"},"reference-count":220,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>C-C motif chemokine ligand 2 (CCL2) interacts with cytokines, adipokines, miRNAs, and multiple synovial cell populations. Experimental studies indicate that these interactions can form a CCL2-associated inflammatory amplification network across cell types. In cellular and animal models, increased CCL2 is associated with monocyte recruitment, synovial fibroblast activation, osteoclast-related bone remodelling, and vascular responses. Therapeutic strategies targeting the CCL2-centered inflammatory network include antagonists of the CCL2\/CCR2 axis, natural products, synthetic compounds, conventional antirheumatic drugs, and emerging delivery-based approaches. Notably, direct CCL2\/CCR2 inhibition has shown biological activity in experimental models but has not produced consistent clinical benefit in established rheumatoid arthritis (RA). Although these findings do not establish CCL2 as a dominant causal driver of RA, human observational studies suggest that circulating CCL2 may complement established markers in preclinical RA risk assessment, disease activity and remission classification, estimation of treatment response, and evaluation of RA-related complications such as interstitial lung disease. Of note, no validated concentration cut-off or standardized assay currently supports its routine clinical use. This review examines the CCL2-related inflammatory network in RA and evaluates its cellular mechanisms, therapeutic implications, and potential clinical applications.<\/jats:p>","DOI":"10.3390\/cells15161461","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"1461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CCL2 in Rheumatoid Arthritis: A Context-Dependent Cross-Cellular Node Serving as Biomarker and Therapeutic Target"],"prefix":"10.3390","volume":"15","author":[{"given":"Bowen","family":"Shi","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Bai","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College, Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanzhen","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2076-6550","authenticated-orcid":false,"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15495","DOI":"10.1007\/s00210-025-04191-y","article-title":"Unveiling the pharmacological mechanisms of Spirulina platensis in rheumatoid arthritis rats through the integration of serum metabolomics, pathways analysis, and experimental validation","volume":"398","author":"Ghallab","year":"2025","journal-title":"Naunyn Schmiedebergs Arch. 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