Metabolic reprogramming of glycolysis favors cartilage progenitor cells rejuvenation

Osteoarthritis (OA), the leading cause of disability in the elderly, still lacks effective treatment due to the unelucidated mechanisms of pathogenesis and progression. In cartilage, although the solo cell type of chondrocytes is resident, cartilage progenitor cells (CPCs) are identified. Chondrocytes in cartilage mainly utilize glycolysis because of the low oxygen tension. Until now, whether the metabolic pathway changes are associated with OA initiation or progression, as well as the biology of CPCs, remains fully clarified. By reviewing relevant literature from previous functional studies, we further mined recently published mouse and human chondrocytes single-cell RNA-sequencing datasets to explore gene expression profiles shift in OA initiation or during OA progression, regarding metabolism. In this review, we demonstrated that chondrocytes' metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) in OA initiation or during OA progression. Genes that related to OXPHOS, electron transport, mitochondrial translation, and mitochondrial respiratory chain complex assembly were upregulated in chondrocytes of injured cartilage or during OA progression. In addition, compared to OXPHOS, glycolysis facilitates CPC expansion and chondrogenic potential. The collated information suggests a potential therapeutic for OA through metabolic reprogramming of glycolysis to interrupt OA pathology and favor CPCs rejuvenation to restore healthy cartilage.