IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways

Zhang, M.; Zhou, Quan; Liang, Qianqian; Li, C.-G.; Holz, Jonathan D.; Tang, Dezhi; Sheu, Tzong‐Jen; Li, T.-F.; Shi, Qi; Wang, Y.-J.

doi:10.1016/j.joca.2008.05.007

Cited by 80 publications

(66 citation statements)

References 30 publications

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“…IGF1 inhibited IL-1β-induced activation of NF-kB and apoptosis of chondrocytes partly through inhibiting phosphorylation, degradation and kinase activity of IkBα, which consequently inhibited NF-kB-mediated expression of some inflammation- and apoptosis-related genes [33], [41]. Meanwhile, IGF-1 also helped to retain the typical features in chondrocytes and enhances synthesis and release of PGs and collagen II mainly through activation of PI3K/Akt signaling pathway [29], [41], [42].…”

Section: Discussionmentioning

confidence: 99%

Angelica Sinensis Polysaccharides Stimulated UDP-Sugar Synthase Genes through Promoting Gene Expression of IGF-1 and IGF1R in Chondrocytes: Promoting Anti-Osteoarthritic Activity

Wen

Tan

et al. 2014

PLoS ONE

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BackgroundOsteoarthritis (OA) is a chronic joints disease characterized by progressive degeneration of articular cartilage due to the loss of cartilage matrix. Previously, we found, for the first time, that an acidic glycan from Angelica Sinensis Polysaccharides (APSs), namely the APS-3c, could protect rat cartilage from OA due to promoting glycosaminoglycan (GAG) synthesis in chondrocytes. In the present work, we tried to further the understanding of ASP-3c’s anti-OA activity.Methodology/Principal FindingsHuman primary chondrocytes were treated with APS-3c or/and recombinant human interleukin 1β (IL-1β). It turned out that APS-3c promoted synthesis of UDP-xylose and GAG, as well as the gene expression of UDP-sugar synthases (USSs), insulin like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), and attenuated the degenerative phenotypes, suppressed biosynthesis of UDP-sugars and GAG, and inhibited the gene expression of USSs, IGF1 and IGF1R induced by IL-1β. Then, we induced a rat OA model with papain, and found that APS-3c also stimulated GAG synthesis and gene expression of USSs, IGF1 and IGF1R in vivo. Additionally, recombinant human IGF1 and IGF1R inhibitor NP-AEW541 were applied to figure out the correlation between stimulated gene expression of USSs, IGF1 and IGF1R induced by APS-3c. It tuned out that the promoted GAG synthesis and USSs gene expression induced by APS-3c was mediated by the stimulated IGF1 and IGF1R gene expression, but not through directly activation of IGF1R signaling pathway.Conclusions/SignificancesWe demonstrated for the first time that APS-3c presented anti-OA activity through stimulating IGF-1 and IGF1R gene expression, but not directly activating the IGF1R signaling pathway, which consequently promoted UDP-sugars and GAG synthesis due to up-regulating gene expression of USSs. Our findings presented a better understanding of APS-3c’s anti-OA activity and suggested that APS-3c could potentially be a novel therapeutic agent for OA.

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Section: Discussionmentioning

confidence: 99%

Angelica Sinensis Polysaccharides Stimulated UDP-Sugar Synthase Genes through Promoting Gene Expression of IGF-1 and IGF1R in Chondrocytes: Promoting Anti-Osteoarthritic Activity

Wen

Tan

et al. 2014

PLoS ONE

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“…Moreover, the cellular interactions between chondrocytes and BMSCs in monolayer co-culture are likely to be bi-directional. Chondrocyte-secreted factors such as TGF-β, bone morphogenetic proteins and IGF-I may promote chondrogenesis of BMSCs in vitro (35)(36)(37). Yamamoto et al (38) co-cultured nucleus pulposus cells with mesenchymal stem cells and found that mesenchymal stem cells can enhance secretion of TGF-β, IGF-1 and epidermal growth factors from nucleus pulposus cells.…”

Section: Discussionmentioning

confidence: 99%

Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components

Chang

Cui

Fan

2011

Braz J Med Biol Res

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“…The expression of MMP-13 is regulated by MAPKs, NF-jB, and Smad2/3 signaling pathways [42,43]. Among them, ERK1/2, JNK, and p38 [11][12][13] are mainly involved in signaling transduction during the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, ERK1/2, JNK, and p38 [11][12][13] are mainly involved in signaling transduction during the inflammatory process. It was reported that [43] in rat endplate chondrocytes, PI3K pathway was involved in the expression of type-II collagen while ERK pathway was involved in the expression of MMP-13. The pomegranate fruit extract (PFE) was reported [44] to inhibit the expression of MMP-13 in the OA cartilage via NF-jB and JNK/p38.…”

Section: Discussionmentioning

confidence: 99%

Effect of Low-Intensity Pulsed Ultrasound on MMP-13 and MAPKs Signaling Pathway in Rabbit Knee Osteoarthritis

Chen

et al. 2011

Cell Biochem Biophys

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We evaluated the effect of low-intensity pulsed ultrasound (LIPUS) on MMP-13 and MAPKs expression in rabbit knee osteoarthritis (OA). For this purpose, 18 New Zealand white rabbits were randomly and equally divided into O + L, O - L, and SO groups. In O + L group, animals underwent right back leg ACLT operation and LIPUS radiation. In O - L group, animals underwent ACLT but no LIPUS treatment. In SO (control) group, animals underwent sham operation without LIPUS. After 6 weeks, we assessed the pathologic changes in the articular surface of femoral condyle and compared using Mankin scores. Also, expression of type-II collagen, MMP-13, ERK1/2, p38, and JNK was measured by Western blot. Compared with controls, Mankin scores were higher in O + L (P < 0.05)/O - L (P < 0.01) groups. Compared with O + L group, score was higher in O - L group (P < 0.05). Compared with controls, type-II collagen expression was less in O + L/O - L groups, with more significant decrease in O - L group (P < 0.05). Contrarily, expression of MMP-13, p-ERK1/2, and p-p38 was enhanced in O + L/O - L groups as compared with controls, with more significant increase in O - L group (P < 0.01). Compared with O + L group, expression was higher in O - L group (P < 0.05). We, therefore, concluded that LIPUS application promoted cartilage repair in OA through the downregulation of MMP-13, ERK1/2, and p38.

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IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways

Abstract: In rat endplate chondrocytes the PI3K pathway mainly transduces IGF-1 effect on col2 expression while the ERK pathway mediates IGF-1 effect on MMP-13 expression.

Cited by 80 publications

References 30 publications

Angelica Sinensis Polysaccharides Stimulated UDP-Sugar Synthase Genes through Promoting Gene Expression of IGF-1 and IGF1R in Chondrocytes: Promoting Anti-Osteoarthritic Activity

Angelica Sinensis Polysaccharides Stimulated UDP-Sugar Synthase Genes through Promoting Gene Expression of IGF-1 and IGF1R in Chondrocytes: Promoting Anti-Osteoarthritic Activity

Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components

Effect of Low-Intensity Pulsed Ultrasound on MMP-13 and MAPKs Signaling Pathway in Rabbit Knee Osteoarthritis

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