Impact of glycogen synthase kinase-3ß inhibition on rats’ temporomandibular joint collagen-induced rheumatoid arthritis with correlation to miRNA-155/miRNA-24 expression

R.H. Al-Serwi, G. Othman, A.F. Dawood, A.K. Alhumaidan, H.S. Alharbi, M. El-Sherbiny, M.E. Almadani, D.M.A. Elsherbini

Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. dmelsherbini@ju.edu.sa

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• Molecular Biology

OBJECTIVE: The current study considered assessing the role of miRNA-155 and miRNA-24 in collagen-induced rheumatoid arthritis (RA) in rats’ temporomandibular joint (TMJ). Their role in histological aggressiveness of the disease and therapy response to glycogen synthase kinase (GSK) inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) will be studied.

MATERIALS AND METHODS: Rats were randomly distributed to four groups (8 rats/group): group I negative control, group II collagen-induced rheumatoid arthritis (CIA), group III Control+TDZD-8 treated group, and group IV CIA+TDZD-8 treated group. Then were euthanized 42 days after the start of the experiment. H&E staining, Masson trichrome staining, and immunohistochemical antibodies against S100 were performed. qRT-PCR of miRNA-155 and miRNA-24 were done for frozen synovial tissues.

RESULTS: Histological analysis showed that the most affected structure in induced rheumatoid arthritis of TMJ is the articular disc, condylar head, and subchondral bone. Combined treatment with TDZD-8 improved histological status in the joint. Masson’s trichrome (MTC) histochemical staining revealed disarrangement of collagen fibers and adherence between the articular disc and condylar cartilage. Meanwhile, the morphology and collagen composition of the disc and condyle in CIA+ TDZD-8 were similar to those of healthy tissues. Immunohistochemical analysis for S100A4 revealed increased immunoreactivity staining in the CIA group. The immunoreactivity was significantly decreased in CIA+ TDZD-8 treated group. TDZD-8 significantly decreased the levels of miRNA-155 and miRNA-24 in synovial tissue.

CONCLUSIONS: Our results reveal for the first-time correlation of miRNA-155 and miRNA-24 that might be implicated in the onset of TMJ RA. Consequently, the treatment of CIA with GSK inhibitor (TDZD-8) yields encouraging results. We predicted the TDZD-8 might protect against CIA by suppressing miRNA-155, miRNA-24, and S100A4 protein levels.

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