Omentin-1 promotes mitochondrial biogenesis via PGC1α-AMPK pathway in chondrocytes

Abstract

Objective Omentin-1 is a newly discovered metabolic regulatory adipokine. Studies have shown that omentin-1 possesses pleiotropic effects in different types of cells. This study aims to investigate the regulation by omentin-1 on mitochondrial biogenesis in chondrocytes. Methodology C-28/I2 chondrocytes were treated with omentin-1 (150 and 300 ng/ml) for 24 h. The expression of mitochondrial regulators, markers and the DNA copy was assessed. The mitochondrial morphology was observed by electron microscopy. The mitochondrial respiratory rate and ATP production in chondrocytes were measured by cell lysates. Results Omentin-1 treatment up-regulated PGC-1α, NRF-1 and mitochondrial transcription factor A (TFAM) in cultured chondrocytes, indicating that omentin-1 could be involved in the regulation of mitochondrial function. Omentin-1 promoted mtDNA/nDNA and four mitochondrial genes (Tomm20, Tomm40, Timm9 and Atp5c1), mRNA transcripts as well as two mitochondrial protein expressions (SDHB and MTCO1). At a cellular level, omentin-1 enhanced the mitochondrial respiratory rate and ATP production. Mechanistically, we proved that omentin-1 increased AMPKα activation, and the blockage of AMPKα by its inhibitor compound C abolished the inductive effect of omentin-1 on PGC1α expression and mtDNA/nDNA ratio, indicating that the effect of omentin-1 is dependent on AMPKα activation. Conclusion Omentin-1 is a positive regulator of mitochondrial biogenesis in chondrocytes, and its action is dependent on the AMPK-PGC1α pathway. This study, therefore, implies that omentin-1 has the potential to remedy chondrocyte damage in the prevention and treatment of osteoarthritis.