C-Reactive Protein Knockout Attenuates Temporomandibular Joint Inflammation in Rats

Abstract

Background. C-reactive protein (CRP), a biomarker of inflammation, is highly expressed in osteoarthritis- (OA-) related diseases, but its exact role remains unknown. In this study, we evaluated the biological effect of CRP on temporomandibular joint (TMJ) inflammation. Methods. Freund’s complete adjuvant (CFA) was used to induce TMJ inflammation in CRP-knockout (CRP-/-) and control rats. Degenerative changes in the TMJ were compared to elucidate the role of CRP in TMJ inflammation. In addition, inflammatory cytokines, macrophage activation, and osteoclast differentiation were evaluated by real-time quantitative polymerase chain reaction, immunohistochemistry, and tartrate-resistant phosphatase staining to explore the potential regulatory mechanism. Results. Compared to the control, CFA induced TMJ inflammation, which increased systemic and local CRP expression. Furthermore, CRP-/- rats exhibited less severe inflammatory symptoms. The downregulation of proinflammatory cytokines (interleukin- (IL-) 1β and IL-6) and upregulation of the anti-inflammatory cytokine IL-10 were detected in CRP-/- rats, which also exhibited reduced macrophage activation and osteoclast differentiation. Conclusion. These results indicated that controlling the highly elevated levels of CRP during inflammation could modify the cytokine profile, macrophage activation, and osteoclast differentiation, thus, providing beneficial effects for TMJ-OA prevention and treatment.

Identification Bioactive Compound of Ethanol-Water Fraction of Coleus atropurpureus for Anti-rheumatic Rheumatism in CFA-induced Rats

“…CFA-induced arthritis in mice is correlated with an increase in plasma levels of CRP (He et al, 2022). The EWC did not significantly reduce the inflammation and autoimmune biomarkers in the EWC treatment groups.…”

Potential pathological and molecular mechanisms of temporomandibular joint osteoarthritis

“…Inflammation is believed to be one of the most crucial factors in the pathological changes in TMJ OA. 4 It has been elucidated that several cytokines, including interleukin (IL) -1β, IL-6, IL-8, IL-17, and tumor necrosis factor (TNF) -α, are elevated in TMJ synovial fluid of TMJ OA patients. 4 , 5 , 6 Among them, IL-1β plays a pivotal role in exacerbating the pathological process of TMJ OA by promoting the release of matrix-degrading enzymes, inhibiting the differentiation of mesenchymal stem cells and mediating the crosstalk between several pro-inflammatory molecules and pathways.…”

“… 4 It has been elucidated that several cytokines, including interleukin (IL) -1β, IL-6, IL-8, IL-17, and tumor necrosis factor (TNF) -α, are elevated in TMJ synovial fluid of TMJ OA patients. 4 , 5 , 6 Among them, IL-1β plays a pivotal role in exacerbating the pathological process of TMJ OA by promoting the release of matrix-degrading enzymes, inhibiting the differentiation of mesenchymal stem cells and mediating the crosstalk between several pro-inflammatory molecules and pathways. 5 , 7 , 8 , 9 The expression of cyclooxygenase (COX) -2 and prostaglandin (PG) E2 is increased in fibroblast-like synoviocytes (FLS) derived from TMJ stimulated with IL-1β, resulting in the activation of ptgs-2/PGE2 pathway and inhibiting the proteoglycan production.…”

Loss of β-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis

“…Although the explicit etiology of TMJOA is poorly understood, there are multiple risk factors, including estrogen, chondrocyte apoptosis, and excessive mechanical stress, contributing to the initiation and progression of TMJOA [ 8 ]. In addition, inflammation has been recognized as an important player in the pathogenesis of TMJOA [ 9 ]. It is widely accepted that TMJOA is a low-inflammatory arthritic condition [ 8 ].…”

“…It is widely accepted that TMJOA is a low-inflammatory arthritic condition [ 8 ]. Various proinflammatory cytokines, including interleukin IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF) -a, were proved to be elevated in temporomandibular joint (TMJ) synovial fluid of TMJOA patients [ 9 , 10 ]. Therefore, an effective control of inflammatory response in TMJOA might be an important therapeutic target for this disease.…”