Distinct expression of SREBP-2 in normal and osteoarthritic chondrocytes

Abstract

Purpose: Recent reports have elucidated that osteoarthritis (OA) is a metabolic disease with the epigenetic and proteomic analysis studies for various lipid metabolism-related genes and proteins comparing osteoarthritic cartilage with normal. Sterol regulatory element-binding protein 2 (SREBP2) is a ubiquitously expressed transcription factor that controls cholesterol homeostasis by stimulating transcription of sterol-regulated genes, such as 3-hydroxy-3-methyl glutaryl CoA reductase (HMGCR) [1]. Apart from regulating cholesterol homeostasis, several studies have provided evidence that SREBP2 and its various single nucleotide polymorphisms (SNPs) also play an central role in the pathogenesis of osteoarthritis, however, the association of SREBP2 with articular chondrocytes arthritogenic effects of IL-1beta (IL-1β) has been poorly understood [2, 3]. In this study, we investigated the association between SREBP2 expression and IL-1β-induced articular chondrocytes arthritogenic effects. Methods: Human cartilage were obtained from total knee arthroplasty for osteoarthritis or total hip arthroplasty for fracture of neck of femur (normal control group). Meanwhile, the normal and osteoarthritic cartilage isolated from of C57BL/6 mice and surgically induced osteoarthritis models. Then, immunohistochemistry staining and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of SREBP2, HMGCR, SOX9, type II collagen and type X collagen. Moreover, we treated normal chondrocytes with different concentration of IL-1β, and examined the expression of the above genes. Results: We found that the expression of SREBP-2, HMGCR, SOX9, type II collagen and type X collagen in OA patients and normal controls were significantly different, and similar results obtained in the two C57BL/6 mice groups. After induced by IL-1β, normal chondrocytes turned hypertrophy-like chondrocytes, and notably, the expression of SREBP-2, type X collagen and HMGCR were upregulated, and SOX9 and type II collagen were suppressed in vitro. Conclusions: These data suggest that SREBP-2 has a distinct expression in normal and osteoarthritic chondrocytes. Proinflammatory cytokine IL-1β may influence the hypertrophy and function of chondrocyte in part through SREBP-2.