TGF-β2 enhances glycolysis in chondrocytes via TβRI/p-Smad3 signaling pathway

Abstract

Chondrocytes rely heavily on glycolysis to maintain the metabolic homeostasis and cartilage matrix turnover. Glycolysis in chondrocytes is remodeled by diverse biochemical and biomechanical factors due to the sporty joint microenvironment. Transforming growth factor-β2 (TGF-β2), one of the most abundant TGF-β superfamily members in chondrocytes, has increasingly attracted attention in cartilage physiology and pathology. Although previous studies have emphasized the importance of TGF-β superfamily members on cell metabolism, whether and how TGF-β2 modulates glycolysis in chondrocytes remains elusive. In the current study, we investigated the effects of TGF-β2 on glycolysis in chondrocytes and explored the underlying biomechanisms. The results showed that TGF-β2 could enhance glycolysis in chondrocytes by increasing glucose consumption, up-regulating liver-type ATP-dependent 6-phosphofructokinase (Pfkl) expression, and boosting lactate production. The TGF-β2 signal entered chondrocytes via TGF-β receptor type I (TβRI), and activated p-Smad3 signaling to regulate the glycolytic pathway. Subsequent experiments employing specific inhibitors of TβRI and p-Smad3 further substantiated the role of TGF-β2 in enhancement of glycolysis via TβRI/p-Smad3 axis in chondrocytes. The results provide new understanding of the metabolic homeostasis in chondrocytes induced by TGF-β superfamily and might shed light on the prevention and treatment of related osteoarticular diseases.