Impact of glycogen synthase kinase-3ß inhibition on rats' temporomandibular joint collagen-induced 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.

Cross-talk between apelin and vasopressin in response to different osmotic stimuli in type 2 diabetic rats.

Apelin, a peptide hormone that has been linked to insulin resistance, obesity and glucose metabolism, coexists with arginine vasopressin (AVP) in hypothalamic magnocellular neurons that control body fluid homeostasis. The significant correlation between serum glucose and serum osmolarity in uncontrolled DM indicates the need for adequate compensation, but how apelin and AVP contribute to this is still unsettled. This study aims to investigate the interaction between apelin and AVP in osmotic regulation in type 2 diabetes mellitus (T2DM), and to explore the underlying mechanism. Forty-eight adult male albino rats were divided into six groups: control (isotonic, ip 0.9% NaCl; hypotonic, ip distilled water; hypertonic, ip 2% NaCl) groups and T2DM (isotonic, hypotonic, hypertonic) groups. Serum levels of AVP, apelin, Na, glucose, serum and urine osmolarity were measured; kidney samples were taken for Aquaporin 2 channels (AQP2) and epithelial sodium channel gamma subunit (ENaCγ) gene expression. Hypothalamic tissue sections were used for immunohistochemical staining of apelin and AVP. Both in control and diabetic groups serum apelin, showed a significant negative correlation with serum AVP (r=-0.533, p≤ 0.001). Serum apelin and AVP were inversely proportional to their hypothalamic protein expression. Serum apelin and AVP were significantly higher in diabetic rats (P= 0.001) yet their percentage change in response to hypo and hyper-osmotic stimuli (1.5±0.7, -0.34±0.15 and -0.38±0.13, 1.95±0.36, respectively) was less pronounced when compared to control rats (3.28±0.52, -0.59±0.12 and -0.45±0.13, 2.58±0.93, respectively). Na and ENaCγ levels significantly increased in hypertonic rats, while AQP2 gene expression significantly increased in hypotonic rats. Both apelin and AVP reacted to osmotic stimuli in T2DM but with less sensitivity than in control rats. In spite of its abnormal increased levels in diabetic rats, apelin maintained its role through counteracting AVP action.