Abstract
Mechanical overloading is a key initiating condition for temporomandibular joint (TMJ) osteoarthritis (OA). The integrin-focal adhesion kinase (FAK) signaling axis is implicated in the mechanobiological response of cells through phosphorylation at Tyr397 (pFAK) but poorly defined in TMJ health and disease. We hypothesize that mechanical overloading disrupts TMJ homeostasis through dysregulation of FAK signaling. To assess if FAK and pFAK are viable clinical targets for TMJ OA, peri-articular tissues were collected from patients with TMJ OA receiving a total TMJ replacement. To compare clinical samples with preclinical in vivo studies of TMJ OA, the joints of c57/bl6 mice were surgically destabilized and treated with and without inhibitor of pFAK (iFAK). FAK signaling and TMJ OA progression was evaluated and compared using RT-PCR, western blot, immunohistochemistry, and histomorphometry. To evaluate mechanical overloading in vitro, primary murine mandibular fibrochondrocytes were seeded in a 4% agarose-collagen scaffold and loaded in a compression bioreactor with and without iFAK. FAK/pFAK was mostly absent from the articular cartilage layer in the clinical sample and suppressed on the central condyle and elevated on the lateral and medial condyle in murine TMJ OA. In vitro, compressive loading lowered FAK/pFAK levels and elevated the expression of TGFβ, NG2, and MMP-13. iFAK treatment suppressed MMP13 and Col6 and elevated TGFβ, NG2, and ACAN in a load independent manner. In vivo, iFAK treatment moderately attenuated OA progression and increased collagen maturation. These data illustrate that FAK/pFAK is implicated in the signaled dysfunction of excessive mechanical loading during TMJ OA and that iFAK treatment can moderately attenuate the progression of cartilage degeneration in the mandibular condyle.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.