Cyclic Tensile Strain Reduces TNF‐α Induced Expression of MMP‐13 by Condylar Temporomandibular Joint Cells

Abstract

To investigate whether the disproportionate degradation of mandibular condyle cartilage in arthritic juvenile temporomandibular joint (TMJ) is related to distinctive responses of TMJ-derived cells to tumor necrosis factor-α (TNF-α), and whether mechanical loading affects this response. The effect of TNF-α (0.1-10 ng/ml) was tested on juvenile porcine TMJ cells isolated from the condyle, fossa, and disc, grown in 3D agarose gels. Expression of anabolic and catabolic factors was quantified by RT-qPCR and/or immunohistochemistry. Condylar cells were stimulated for 12 h with TNF-α (10 ng/ml), followed by 8 h of 6% cyclic tensile strain, and gene expression of MMPs was quantified. TNF-α (10 ng/ml) reduced the expression of the matrix proteins collagen types I and II after 6 h of incubation. Aggrecan gene expression was increased in the presence of 0.1 ng/ml TNF-α. The fossa and disc cells responded to TNF-α with an increased expression of the aggrecanase ADAMTS4. TNF-α enhanced MMP-13 gene and protein expression only by condylar cells. Mechanical loading reduced this effect. Cells isolated from the different cartilaginous structures reacted differently to TNF-α. Since the disc and fossa contain a very low level of proteoglycans in comparison to the condyle, the role played by ADAMTS4 in degradation of the fossa and disc might be limited. TNF-α induced MMP-13 expression by condylar cells might be involved in the degradation of the juvenile condyle. Since this expression was reduced by mechanical loading, functional loading with oral physiotherapy or orthodontic activators may help to reduce the catabolic effect of TNF-α. J. Cell. Physiol. 232: 1287-1294, 2017. © 2016 Wiley Periodicals, Inc.

The many faces of genetic contributions to temporomandibular joint disorder: An updated review

“…Associated with disc degeneration, degradation of the juvenile condyle and decreased expression in hyperplasia…”

“…Genes involved in structural functions, such as ACTN3 (alpha‐actinin‐3), GSTM1 (glutathione S ‐transferase mu 1), MTHFD (C‐1‐tetrahydrofolate synthase, cytoplasmic) and MTRR (methionine synthase reductase), may influence the risk of temporomandibular dysfunction . We can speculate that these genes possibly respond differently to oxidative stress, which leads to the production of nitrous oxide and peroxynitrite, reacts to excessive mechanical overload, and is harmful to DNA, which could promote greater susceptibility to TMD.…”

“…Matrix metalloproteinases ( MMPs ) are also involved in cartilage degradation that involves internal derangement of TMJ . The rs1799750 2G2G genotype in particular seems to be associated with disc displacement without reduction and, most importantly, seems to worsen this degenerative condition, which may explain why some patients respond negatively to treatment …”

Relationship between arthroscopic findings of synovitis and levels of tumour necrosis factor‐alpha and matrix metalloproteinases in synovial lavage fluid from patients with unilateral high mandibular condyle fractures

“…Several previous reports have also indicated that TNF-alpha induces the expression of MMPs; [22][23][24] Arthrocentesis has an effect of washing out inflammatory products that accumulate in the joint compartment of a dysfunctional TMJ. 20,26 The procedure removes inflammatory cytokines, which are pain-causing substances, for early reduction in TMJ pain and quick recovery of jaw function in patients with a high mandibular condyle fracture, thus increasing the possibility of a successful rehabilitation.…”

“…Also, when the relationship between TNF‐alpha and MMPs was examined, the expression of TNF‐alpha in patients with a high mandibular condyle fracture was shown to be not coincidental. Several previous reports have also indicated that TNF‐alpha induces the expression of MMPs; thus, the concentrations of MMP‐3, MMP‐9 and MMP‐13 in particular were investigated in this study for their relationship to TMJ pathology.…”