Phosphatase and tensin homolog accelerate the inflammatory injury and glycolysis of chondrocytes through TP53 protein-mediated p38MAPK pathway activation in a high-glucose environment.

OBJECTIVE: Chronic metabolic diseases represent a high-risk factor for osteoarthritis. In particular, diabetes has been proven to be closely related to the occurrence of osteoarthritis in cases called diabetic osteoarthritis (DAO). A large number of studies have shown that phosphatase and tensin homolog (PTEN) are involved in the progression of osteoarthritis; however, the mechanism of PTEN in DAO remains unclear. Accordingly, this study aimed to explore the regulatory role of PTEN in inflammatory injury and glycolysis during the progression of DAO. MATERIAL AND METHODS: Primary chondrocytes treated with high glucose (HG) were transfected with the small interfering (si) RNA of PTEN or tumor suppressor protein p53 (TP53). Then, cell viability and apoptosis, inflammatory factor secretion, and the protein expression of matrix metalloproteinase 13 and collagen II were detected. Subsequently, we examined glucose uptake, lactate production, reactive oxygen species (ROS) content, and the protein expression of glycolysis-related molecules, namely hexokinase2 and lactate dehydrogenase A, in PTEN knockdown primary chondrocytes. Then, primary chondrocytes were transfected with siRNA against PTEN (siPTEN) alone or together with plasmid DNA (pcDNA)-TP53 to detect changes in cellular inflammatory damage and glycolysis, and thus, determine whether the p38 mitogen-activated protein kinase (p38MAPK) pathway affects the inflammatory damage and glycolysis of chondrocytes by introducing SB203580, which is a p38 pathway inhibitor. RESULTS: PTEN protein expression was up-regulated (P < 0.05) in rat primary chondrocytes in an HG environment, accompanied by decreased cell viability (P < 0.05), increased apoptosis (P < 0.05), increased secretion of inflammatory factors (P < 0.05), and aggravated degradation of the cell matrix (P < 0.05). In addition, HG-treated chondrocytes exhibited abnormal metabolism, which was manifested by increased glucose uptake (P < 0.05), lactate content (P < 0.05), ROS generation (P < 0.05), and expression of glycolysis-related molecules (P < 0.05). Meanwhile, the transfection of si-PTEN inhibited PTEN protein expression and reversed the inflammatory injury and glycolysis of chondrocytes caused by an HG environment. TP53 is a PTEN-binding protein, and its expression is positively regulated by PTEN. Similar to the role of PTEN, TP53 silencing reversed the inflammatory injury (P < 0.05) and glycolysis (P < 0.05) of chondrocytes caused by an HG environment. Further mechanistic studies have shown that PTEN promotes the inflammatory injury (P < 0.05) and glycolysis (P < 0.05) of chondrocytes by up-regulating the expression of TP53. Moreover, by introducing SB203580, a p38 pathway inhibitor, we confirmed that this process was mediated by activating the p38MAPK pathway. CONCLUSION: PTEN accelerates the inflammatory injury and glycolysis of chondrocytes through the activation of the TP53 protein-mediated p38MAPK pathway in an HG environment.