Long non-coding RNA (LncRNA) small nucleolar RNA host gene 1 (SNHG1) has been reported in the occurrence and development of several diseases, but its biological role and mechanism in osteoarthritis (OA) remain to be illuminated. In the present research, we aimed to investigate the effect of SNHG1 on IL-1β-induced OA and its molecular mechanism. Results revealed that SNHG1 decreased the expression of MMPs, ADAMTs, collagen, and aggrecan, and ameliorates IL-1β-induced metabolic dysfunction in normal human chondrocytes-keen. In addition, SNHG1 inhibited the expressions of pro-inflammatory cytokines in chondrocytes, including NO, PGE2, IL-6, TNF-α, i-NOS, and COX-2. Furthermore, luciferase reporter assay demonstrated that SNHG1 could directly interact with miR-16-5p and suppressed miR-16-5p expression and activity. What is more, miR-16-5p overexpression reversed SNHG1-inhibited aberrant catabolism and inflammation triggered by IL-1β stimulation. Finally, SNHG1 inhibits the expression of miR-16-5p-mediated factors involved in p38MAPK and NF-κB signaling pathways, including ERK1/2, p-p38 and p-p65. Taken together, the results of our studies illuminate that SNHG1 alleviates the inflammation of IL-1β-induced OA through the activation of miR-16-5p-mediated p38MAPK and NF-κB signaling pathway. It suggested that SNHG1 may serve as a potential target for OA diagnosis and treatment.
Glycolytic disorder has been demonstrated to be a major cause of osteoarthritis (OA) and chondrocyte dysfunction. The present work aimed to investigate the expression and role of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in OA cartilage. It was found that PFKFB3 expression was down-regulated in human OA cartilage tissues and in tumour necrosis factor (TNF)-α- or interleukin (IL)-1β-stimulated human chondrocytes. The glycolytic metabolism appeared as glucose utilization and adenosine triphosphate (ATP) generation, and lactate production was stunted in OA cartilage. However, the impaired glycolytic process in OA cartilage was improved by PFKFB3 overexpression, which was confirmed in TNF-α- or IL-1β-treated chondrocytes. Furthermore, the expressions of endoplasmic reticulum (ER) stress-associated genes including PERK, ATF3, IRE1, phosphorylated eIF2α (p-eIF2α) and MMP13 were enhanced in OA cartilage explants, while they were decreased by AdPFKFB3 transfection. PFKFB3 also modulated the expressions of PERK, ATF3, IRE1, p-eIF2α and MMP13 in tunicamycin-exposed chondrocytes. Additionally, PFKFB3 improved the cell viability of OA cartilage explants and chondrocytes through the PI3K/Akt/C/EBP homologous protein (CHOP) signalling pathway. The transfection of AdPFKFB3 also significantly reduced caspase 3 activation and promoted aggrecan and type II collagen expressions in OA cartilage explants and chondrocytes. In all, this study characterizes a novel role of PFKFB3 in glycolytic metabolism and ER stress of OA cartilage explants and chondrocytes. The study might provide a potential target for OA prevention or therapy.
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