Chemokine (C-C Motif) Ligand 2/Chemokine Receptor 2 (CCR2) Axis Blockade to Delay Chondrocyte Hypertrophy as a Therapeutic Strategy for Osteoarthritis

Abstract

Background Chondrocytes play a vital role in the later stages of osteoarthritis (OA). The roles of chemokine (C-C motif) ligand 2 (CCL2) and its receptor, chemokine receptor 2 (CCR2), are as yet poorly elucidated in chondrocyte hypertrophy (CH). Here, we aimed to regulate the CCL2/CCR2 axis and explore its effect on progression of CH. Material/Methods Chondrocytes isolated from patients with OA were used in the present study. In vitro experiments were conducted to test hypertrophic gene and CCL2/CCR2 expression in chondrocyte degeneration caused by interleukin (IL)-17A or CCL2 protein stimulation. In addition, inhibition of CCL2 and CCR2 was used to assess the role of CCL2 and CCR2 blockade in CH. Relative gene expression was determined with real-time polymerase chain reaction, western blot, or immunofluorescence. Hypertrophic changes were assessed with cell area measurement. Moreover, the viability of chondrocytes was analyzed using an MTT assay and flow cytometry was used to assess cell apoptosis. Results CCL2 and CCR2 were upregulated in IL-17A-treated chondrocytes. The exogenic CCL2 stimulation also promoted CH and increased the expression of Type 10 collagen, RUNX2 , and IHH , which could be reversed via suppression of CCR2. Inhibition of CCL2 and CCR2 expression was sufficient to: 1) protect Type 2 collagen synthesis; 2) alleviate IL-17A-induced overexpression of Type 10 collagen, RUNX2 , and IHH ; and 3) improve chondrocyte proliferation and apoptosis. Conclusions Blockading the CCL2/CCR2 axis plays a role in delaying the development of CH.

P-15 promotes chondrocyte proliferation in osteoarthritis by regulating SFPQ to target the Akt-RUNX2 axis

“…Runtassociated transcription factor 2 (RUNX2) is a master transcription factor for chondrocyte hypertrophy that plays an important role in osteoarthritis [10]. Researchers have demonstrated that chondrocyte hypertrophic differentiation, a key process in endochondral ossification, is also a feature of osteoarthritis leading to cartilage destruction [10,11]. In addition, SFPQ could be competitively bound by various non-coding RNAs, thereby increasing the translation level of RUNX2 [12,13].…”

Bioinformatics-based analysis of potential candidates chromatin regulators for immune infiltration in osteoarthritis

“…CCR2 is one of the more studied chemokine receptors in OA. CCR2 is upregulated in interleukin-17A-treated chondrocytes and protects type II collagen synthesis and attenuates the IL-17A-induced overexpression of RUNT-related transcription factor 2 by inhibiting CCR2 expression, thereby delaying the development of chondrocyte hypertrophy [55].…”

The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy

“…Based on the findings of the abovementioned studies, it can be hypothesized that copper cell death genes are crucial for immune infiltration in osteoarthritis; however, there have been few investigations into the involvement of copper cell death-related genes in the immune regulation of osteoarthritis. Antigen-presenting cells, mast cells, dendritic cells, and chemokine receptor 2 (CCR2) may have significant effects on the regulation of copper cell death genes in osteoarthritis [ 118 , 119 , 120 , 121 ] ( Figure 1 ).…”