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

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.