IL-1β Damages Fibrocartilage and Upregulates MMP-13 Expression in Fibrochondrocytes in the Condyle of the Temporomandibular Joint

Abstract

The temporomandibular joint (TMJ), which differs anatomically and biochemically from hyaline cartilage-covered joints, is an under-recognized joint in arthritic disease, even though TMJ damage can have deleterious effects on physical appearance, pain and function. Here, we analyzed the effect of IL-1β, a cytokine highly expressed in arthritic joints, on TMJ fibrocartilage-derived cells, and we investigated the modulatory effect of mechanical loading on IL-1β-induced expression of catabolic enzymes. TMJ cartilage degradation was analyzed in 8–11-week-old mice deficient for IL-1 receptor antagonist (IL-1RA−/−) and wild-type controls. Cells were isolated from the juvenile porcine condyle, fossa, and disc, grown in agarose gels, and subjected to IL-1β (0.1–10 ng/mL) for 6 or 24 h. Expression of catabolic enzymes (ADAMTS and MMPs) was quantified by RT-qPCR and immunohistochemistry. Porcine condylar cells were stimulated with IL-1β for 12 h with IL-1β, followed by 8 h of 6% dynamic mechanical (tensile) strain, and gene expression of MMPs was quantified. Early signs of condylar cartilage damage were apparent in IL-1RA−/− mice. In porcine cells, IL-1β strongly increased expression of the aggrecanases ADAMTS4 and ADAMTS5 by fibrochondrocytes from the fossa (13-fold and 7-fold) and enhanced the number of MMP-13 protein-expressing condylar cells (8-fold). Mechanical loading significantly lowered (3-fold) IL-1β-induced MMP-13 gene expression by condylar fibrochondrocytes. IL-1β induces TMJ condylar cartilage damage, possibly by enhancing MMP-13 production. Mechanical loading reduces IL-1β-induced MMP-13 gene expression, suggesting that mechanical stimuli may prevent cartilage damage of the TMJ in arthritic patients.

Wnt/β-catenin signaling pathway is activated in the progress of mandibular condylar cartilage degeneration and subchondral bone loss induced by overloaded functional orthopedic force (OFOF)

“…The stained sections were analyzed under a Leica DM 2500 microscope. TRAP staining was performed on each slide in each group to assess osteoclast activity (Sigma, USA) [ 6 ]. TRAP staining was used to explore the osteoclast activity of the subchondral bone of the condyle.…”

“…TMD can progress to temporomandibular joint osteoarthritis (TMJ-OA), it will lead to severe dysfunction and pain. The progressive degeneration of mandibular condylar cartilage (MCC) is commonly associated with synovial inflammation and subchondral bone loss, which is the main characteristic of TMJ disease [ 6 ]. Animal models have proofed different processes and degrees of mandibular condylar cartilage degeneration through different overloading forces on TMJ of animal models to build steady mouth opening [ 7 ], occlusal disorder [ 8 ], or resistant food [ 9 ].…”

“…Sclerostin has been shown to be an endogenous Wnt/β-catenin inhibitor that maintains cartilage integrity in a mouse model of OA [ 10 , 17 ]. Another study also suggested that sclerostin plays a protective role by inhibiting Wnt [ 6 ].…”

Emerging Potential of Exosomes in Regenerative Medicine for Temporomandibular Joint Osteoarthritis

“…There is also accumulating evidence that chondrocytes play a major role in the destruction of subchondral bone. The upregulation of catabolic enzymes in cartilage matrix, such as matrix metalloproteinases (MMPs), disintegrins, and MMPs with thrombospondin motifs (ADAMTS), is a result of the pathologic changes of TMJ OA [38]. In addition, the upregulation of ADAMTS-5 was observed in condylar cartilage during early stages of TMJ OA [39].…”

Rapamycin-Induced Autophagy Promotes the Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells in the Temporomandibular Joint in Response to IL-1β

“…As an important inflammatory cytokine in the initiation and development of TMD, IL-1 β was widely used to simulate the inflammatory microenvironment of TMD in vitro[ 10 , 11 ]. In this study, we showed that IL-1 β inhibited the autophagy and chondrogenic differentiation of SMSCs.…”