LncPVT1 promotes cartilage degradation in diabetic OA mice by downregulating miR-146a and activating TGF-ß/SMAD4 signaling.

INTRODUCTION: To investigate the role of LncRNA PVT1 (plasmacytoma variant translocation 1) in hyperglycemia-triggered cartilage damage using the diabetic osteoarthritis (OA) mice model. MATERIALS AND METHODS: Streptozotocin (STZ) was used to induce mouse diabetes. Knee OA model was induced through transection of anterior cruciate ligament (ACLT). Severity of arthritis was assessed histologically by Safranin O-Fast Green Staining using Mankin Scores. LncRNA PVT1 and miR-146a were detected by real-time polymerase chain reaction (PCR) in cartilage tissue. Moreover, the interaction among PVT1, miR-146a, and SMAD4 was examined by luciferase reporter assays. Mice were injected intra-articularly with ad-siRNA-PVT1 and ad-siRNA scramble control. Articular concentrations of TNF-α, IL-1, IL-6 and TGF-ß1 were determined using enzyme-linked immunosorbent assay. Levels of type II Collagen (COL2A1), TGF-ß1, p-SMAD2, SMAD2, p-SMAD3, SMAD3, SMAD4 and nuclear SMAD4 were detected by western blot analysis. RESULTS: PVT1 expression was significantly increased, whereas miR-146a was markedly decreased in diabetic OA mice than in non-diabetic OA and control. Increased PVT1 expression in diabetic OA mice was significantly associated with Mankin score and reduced miR-146a as well as Collagen alpha-1(II) (COL2A1) expressions. In vivo, intra-articular injection of ad-siRNA-PVT1 efficiently increased miR-146a and COL2A1 expressions, alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed TGF-ß/SMAD4 pathway in diabetic OA mice. CONCLUSIONS: Our results demonstrate LncRNA PVT1 is involved in cartilage degradation in diabetic OA and correlated with disease severity. Efficiency of ad-siRNA-PVT1 in controlling joint inflammation in diabetic OA mice is associated with the suppression of the expression of miR-146a, pro-inflammatory cytokines and activation of TGF-ß/SMAD4 pathway.

Possible Involvement of Serum and Synovial Fluid Resistin in Knee Osteoarthritis: Cartilage Damage, Clinical, and Radiological Links.

BACKGROUND: Resistin is an adipocytokine associated with inflammation and insulin resistance. Recent studies have shown that resistin plays an important role in the pathogenesis and progression in osteoarthritis (OA) patients. The current study was aimed at investigating the relationship between resistin in serum and synovial fluid (SF) and disease severity in patients with knee osteoarthritis. METHOD: Seventy-four patients diagnosed with knee OA and 79 healthy controls receiving regular body check in our hospital were recruited in the study. The Noyes score method was used to assess articular cartilage damage arthroscopically. The symptomatic severity was evaluated according to the Western Ontario McMaster University Osteoarthritis (WOMAC) scores. The radiographic disease severity of OA was assessed by the Kellgren-Lawrence (K-L) grading system. The resistin levels in serum and SF were determined by enzyme-linked immunosorbent assay. Cartilage degradation marker CTX-II in SF was also examined. RESULTS: SF but not serum resistin levels are positively associated with Noyes scores, K-L grading scores WOMAC pain scores, physical functional scores and WOMAC total scores. In addition, SF resistin correlated positively with CTX-II. CONCLUSION: Resistin in SF might serve as a potential biomarker for reflecting the disease severity and cartilage degenerative extent of knee OA.