The adipokine LCN2 is regulated in adipocyte and osteoarthritic osteochondral junction
學生姓名:
張恆偉
指導教授:
龔瑞林
學 號:
0013A034
學期:
105上
摘 要:
Osteoarthritis (OA) is a debilitating disease characterized by degradation of articular cartilage and meniscus, osteophyte formation, synovitis and subchondral bone sclerosis. The main risk factors of osteoarthritis include sex, previous injury and genetic factors. Of these risk factors, obesity is beyond doubt considered a prominent one. Obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction. The pro-inflammatory cytokines and adipokines released from adipocytes also influence the progression of osteoarthritis.
Lipocalin-2 (LCN2) is a novel adipokine that negatively impacts articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. The aim of this report is to explore regulation of LCN2 in adipocyte and osteoarthritic osteochondral junction.
The first study investigated the regulation of LCN2 expression in adipose tissue in response to metabolic stress in mice as well as the control of LCN2 expression and secretion by cytokines in 3T3-L1 adipocytes. Results demonstrated that LCN2 production in adipocytes is highly upregulated by metabolic stress and cytokines. Further research on modulation of LCN2 expression in osteochondral junction. Gene overexpression and knockdown were performed using specific expression vectors and siRNA technology, respectively. ELF3 and NF-κB overexpression transactivated the LCN2 promoter and increased the IL-1-induced mRNA and protein levels of LCN2 in human and mouse chondrocytes. The data also showed that LCN2 expression in human osteoblasts and chondrocytes was induced by catabolic and inflammatory factors; however, TGF-β1 and IGF-1 reversed this induction. Then LCN2 reduced osteoblast viability in the presence of iron and enhanced the activity of MMP-9 released by osteoblasts.
In conclusion, LCN2 production in adipocytes is highly responsive to metabolic stress and pro-inflammatory cytokines. Pro-inflammatory cytokine can activate ELF3 and NFκB transcription factors which lead the induction of LCN2 in chondrocytes. LCN2 expression in chondrocytes is regulated in a paracrine manner after osteoblast stimulation.
Lipocalin-2 (LCN2) is a novel adipokine that negatively impacts articular cartilage, triggering catabolic and inflammatory responses in chondrocytes. The aim of this report is to explore regulation of LCN2 in adipocyte and osteoarthritic osteochondral junction.
The first study investigated the regulation of LCN2 expression in adipose tissue in response to metabolic stress in mice as well as the control of LCN2 expression and secretion by cytokines in 3T3-L1 adipocytes. Results demonstrated that LCN2 production in adipocytes is highly upregulated by metabolic stress and cytokines. Further research on modulation of LCN2 expression in osteochondral junction. Gene overexpression and knockdown were performed using specific expression vectors and siRNA technology, respectively. ELF3 and NF-κB overexpression transactivated the LCN2 promoter and increased the IL-1-induced mRNA and protein levels of LCN2 in human and mouse chondrocytes. The data also showed that LCN2 expression in human osteoblasts and chondrocytes was induced by catabolic and inflammatory factors; however, TGF-β1 and IGF-1 reversed this induction. Then LCN2 reduced osteoblast viability in the presence of iron and enhanced the activity of MMP-9 released by osteoblasts.
In conclusion, LCN2 production in adipocytes is highly responsive to metabolic stress and pro-inflammatory cytokines. Pro-inflammatory cytokine can activate ELF3 and NFκB transcription factors which lead the induction of LCN2 in chondrocytes. LCN2 expression in chondrocytes is regulated in a paracrine manner after osteoblast stimulation.
10532014-張恆偉摘要.pdf