Distinct metabolic programs induced by TGF-β1 and BMP2 in human articular chondrocytes with osteoarthritis.

Objectives: Cellular energy metabolism is important for the function of all tissues, including cartilage. Recent studies indicate that superficial and deep subpopulations of articular chondrocytes (ACs) have distinct metabolic profiles. At the cellular and molecular level, osteoarthritis (OA) is characterised by alteration from a healthy homoeostatic state towards a catabolic state. Several molecular pathways, including transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signalling, have been identified as critical players in the pathogenesis and progression of OA. However, the manner in which these factors influence cellular energy metabolism in ACs is not well understood. This study investigates the effect of TGF-β or BMP signalling on energy metabolism in human articular chondrocytes (hACs).

Methods: ACs were isolated from residual macroscopically full thickness and intact cartilage from the femoral condyle of human samples obtained from patients with OA. ACs were treated with Vehicle (control), TGF-β1 or BMP2 for 48-72 hours. Metabolic assays were performed to determine glucose consumption, lactate production and adenosine triphosphate (ATP) production, whereas the mitochondrial stress test was performed to determine oxygen consumption rate. Protein was isolated to assess translational activity and was evaluated using Western blot.

Results: We showed that TGF-β1, known to maintain chondrocyte homoeostasis, stimulated glycolysis by upregulating key glycolytic factors, such as glucose transporter 1 (Glut1) and hexokinase II, while reducing oxidative phosphorylation in hACs. In contrast, BMP2 enhanced mitochondrial metabolism and oxidative phosphorylation and had a minimal effect on key glycolytic regulators.

Conclusions: Our data revealed distinct metabolic programs induced by TGF-β1 and BMP2 in hACs, suggesting that the regulation of cellular metabolism may represent a new mechanism underlying the pathogenesis of OA.

The Translational Potential Of This Article: The findings define the regulation of energy metabolism as a potential novel therapeutic approach for the treatment of OA.