Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jul 15:15:1387651.
doi: 10.3389/fimmu.2024.1387651. eCollection 2024.

Harmonizing hope: navigating the osteoarthritis melody through the CCL2/CCR2 axis for innovative therapeutic avenues

Mitra Abbasifard  1 , Hossein Khorramdelazad  2
Affiliations
Review

Harmonizing hope: navigating the osteoarthritis melody through the CCL2/CCR2 axis for innovative therapeutic avenues

Mitra Abbasifard et al. Front Immunol. .

Abstract

Osteoarthritis (OA) is characterized by a complex interplay of molecular signals orchestrated by the CCL2/CCR2 axis. The pathogenesis of OA has been revealed to be influenced by a multifaceted effect of CCL2/CCR2 signaling on inflammation, cartilage degradation, and joint homeostasis. The CCL2/CCR2 axis promotes immune cell recruitment and tips the balance toward degeneration by influencing chondrocyte behavior. Insights into these intricate pathways will offer novel therapeutic approaches, paving the way for targeted interventions that may redefine OA management in the future. This review article explores the molecular symphony through the lens of the CCL2/CCR2 axis, providing a harmonious blend of current knowledge and future directions on OA treatment. Furthermore, in this study, through a meticulous review of recent research, the key players and molecular mechanisms that amplify the catabolic cascade within the joint microenvironment are identified, and therapeutic approaches to targeting the CCL2/CCR axis are discussed.

Keywords: CCL2; CCR2; autoimmune disease; inflammation; osteoarthritis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Role of the CCL2/CCR2 axis OA immunopathogenesis. Overexpression of CCL2 in chondrocytes and synovial cells is associated with CCR2+ macrophages and T cell recruitments and infiltration in the synovium, chronic inflammation, and OA. CCL2/CCR2 axis regulates inflammation in OA and other pathological conditions, and activation of synovial fibroblasts by pro-inflammatory cytokines leads to CCL2 release and recruitment of CCR2+ monocytes and macrophages. Macrophages play a role in preserving inflammation and inducing cartilage damage via cytokine production (IL-1β, IL-6, TNF-α) and MMP activation. Chondrocytes upregulate CCL2 expression in response to mechanical stress and inflammatory signals, leading to cartilage degeneration. CCR2 facilitates cartilage and bone damage independently of synovial macrophage infiltration. Ultimately, the dysregulation of the CCL2/CCR2 axis can lead to joint inflammation and tissue damage.
Figure 2
Figure 2
Therapeutic approaches targeting the CCL2/CCR2 axis in OA. The figure outlines various strategies targeting the CCL2/CCR2 axis for OA treatment. CCR2 targeting agents include gene inactivation and antagonists like INCB8761, CCX872, RS504393, BMS-813160, BMS-687681, PF-04178903, and CCX140-B, which block inflammatory cell recruitment. CCL2 targeting includes monoclonal antibodies (Carlumab, ABN912), Bindarit (an NF-κB pathway inhibitor), CCN1 siRNA, and Tanshinone IIA (a traditional medicine extract). Dual inhibition strategies combine CCL2/CCR2 inhibitors with TNF-α inhibitors (Etanercept, Adalimumab) or bi-specific antibodies. Combination therapies pair CCL2/CCR2 inhibitors with NSAIDs or DMARDs. Lastly, nanosystems utilize nanoparticles for targeted delivery of these inhibitors, enhancing bioavailability and reducing systemic side effects.
None
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep. (2013) 15:1–10. doi: 10.1007/s11926-013-0375-6 - DOI - PMC - PubMed
    1. Leung GJ, Rainsford K, Kean WF. Osteoarthritis of the hand I: aetiology and pathogenesis, risk factors, investigation and diagnosis. J Pharm Pharmacol. (2014) 66:339–46. doi: 10.1111/jphp.12196 - DOI - PubMed
    1. Musumeci G, Aiello FC, Szychlinska MA, Di Rosa M, Castrogiovanni P, Mobasheri A. Osteoarthritis in the XXIst century: risk factors and behaviours that influence disease onset and progression. Int J Mol Sci. (2015) 16:6093–112. doi: 10.3390/ijms16036093 - DOI - PMC - PubMed
    1. Rainville J, Bono JV, Laxer EB, Kim DH, Lavelle JM, Indahl A, et al. . Comparison of the history and physical examination for hip osteoarthritis and lumbar spinal stenosis. Spine J. (2019) 19:1009–18. doi: 10.1016/j.spinee.2019.01.006 - DOI - PubMed
    1. Swagerty DL, Jr., Hellinger D. Radiographic assessment of osteoarthritis. Am Family Physician. (2001) 64:279–87. - PubMed

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

LinkOut - more resources