Leptin induction of aggrecanases-1 and -2 genes expression in human chondrocytes is mediated by p38 mitogen-activated protein kinase pathway (CCR5P.265)

Abstract

Abstract The cloning of leptin initiated to explore new functions of adipose tissue. The studies revealed that adipose tissue like endocrine organ involves in critical roles by secreting adipokines. Among them, leptin is the most studied and characterized adipokine, and involves in several pivotal processes including inflammation. The degradation of articular cartilage components by aggrecanases-1 and -2 (called also a disintegrin and metalloproteinase with thrombospondin motifs -4 and -5) is a key event for arthritic diseases. The catabolic effect of leptin on articular cartilage degradation by increasing aggrecanases was established, but the pathways involved in this upregulation have not been elucidated. It was aimed to investigate putative molecular pathways involving in the upregulation of aggrecanases by leptin. The cultured human articular chondrocytes were incubated with SB203580 (a specific inhibitor of p38) and subsequently recombinant human leptin. At the end of the 48 hours, total RNA was extracted. The mRNA was reverse-transcribed into cDNA and the expression levels of aggrecanases were analyzed using real-time polymerase chain reaction. The leptin induced aggrecanases expressions were suppressed by SB203580. The elucidation of underlying pathways for aggrecanases upregulation may promote the new approaches for the treatment of arthritic diseases. It can be concluded from our result, p38 MAPK might be one of the potential target for cartilage degradation caused by leptin.