Chemokine (C-C Motif) Ligand 2/Chemokine Receptor 2 (CCR2) Axis Blockade to Delay Chondrocyte Hypertrophy as a Therapeutic Strategy for Osteoarthritis
MEDICAL SCIENCE MONITOR(2021)
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 MU 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 promot- ed 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.
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Key words
Chondrocytes, Hypertrophy, Osteoarthritis
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