Cross-talk of inflammation and chondrocyte intracellular metabolism in osteoarthritis

Osteoarthritis is a disease that impacts millions around the world, leading to significant financial and medical burden for patients and the healthcare system. However, no effective biomarkers or disease modifying therapeutics exist for the early identification and management of the disease. Inflammation drives chondrocytes to express extracellular matrix (ECM) degrading enzymes and interruption of this pathway is a viable target to prevent degradation of cartilage. It has been demonstrated that inflammation can alter the intracellular metabolism of chondrocytes, a process known as metabolic reprogramming. This metabolic reprogramming is critical for cartilage breakdown by shifting chondrocytes to an ECM-catabolic state and likely as a potential therapeutic target for osteoarthritis. Metabolic modulators hold the potential to reduce chondrocyte inflammatory responses and protect cartilage. In this narrative review, we explore some of the existing examples of interactions between metabolism and inflammatory pathways in chondrocytes. We summarize the impact of inflammatory stimulation on various metabolic pathways and describe several examples by which targeting of metabolism is able to modulate ECM-degrading activity of chondrocytes to protect against cartilage damage.