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Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β-induced catabolic gene expression in cartilage.

Sheu SY, Ho SR, Sun JS, Chen CY, Ke CJ - BMC Complement Altern Med (2015)

Bottom Line: The effects of Ecd on IL-1β-induced inflammatory conditions and their related catabolic genes expression were analyzed.With the pre-treatment of 10(-8) M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.In conclusions, Ecd can reduce the IL-1β-induced inflammatory effect of the cartilage.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. amel@tmu.edu.tw.

ABSTRACT

Background: In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1β-induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA.

Methods: Chondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2α (EPAS1) in cartilage catabolism simulated by IL-1β (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1β-induced inflammatory conditions and their related catabolic genes expression were analyzed.

Results: Interleukin-1β (IL-1β) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10(-8) M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.

Conclusion: In conclusions, Ecd can reduce the IL-1β-induced inflammatory effect of the cartilage. Ecd may suppress IL-1β-induced cartilage catabolism via HIF-2α pathway.

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Related in: MedlinePlus

Ecd pre-treatment reduce the catabolic effect of IL-1β on the cartilage explants. Treatment of primary cultures of mouse articular cartilage explants with recombinant mouse IL-1β protein specifically induce the expression of MMP3 (A), MMP13 (B) and ADAMTS-5 (C) genes expression; with the pretreatment of 10−8M Ecd, the catabolic factor genes upregulated by IL-1β treatment are eliminated. (Each value is the mean ± standard deviations; n = 8; *:p<0.05; **:p< 0.01; ***:p < 0.001).
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Fig3: Ecd pre-treatment reduce the catabolic effect of IL-1β on the cartilage explants. Treatment of primary cultures of mouse articular cartilage explants with recombinant mouse IL-1β protein specifically induce the expression of MMP3 (A), MMP13 (B) and ADAMTS-5 (C) genes expression; with the pretreatment of 10−8M Ecd, the catabolic factor genes upregulated by IL-1β treatment are eliminated. (Each value is the mean ± standard deviations; n = 8; *:p<0.05; **:p< 0.01; ***:p < 0.001).

Mentions: The catabolic effect of IL-1β on cartilage explants are mediated via HIF-2α–induced expression of MMP3, MMP13 and ADAMTS-5. The IL-1β related gene expression of primary mouse articular cartilage explants are examined. Same as noted above, IL-1β enhances Epas1 mRNA expression and suppresses collagen type II (Col2a1) gene expression. With the pretreatment of 10−8M Ecd, it can scavenge IL-1β effect on Epas1 gene expression, but there is also no effect on Col2a1 gene expression (Figure 2). IL-1β treatment also specifically up-regulate MMP3, MMP13 and ADAMTS-5 genes expression (Figure 3). The pre-treatment of 10−8M Ecd can effectively down-regulate the catabolic genes expression. Ecd can reduce the catabolic effect of IL-1β on the cartilage explants; Ecd has protective effects on articular cartilage by inhibiting Epas1, MMP-3, MMP-13 and ADAMTS-5 genes expression.Figure 2


Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β-induced catabolic gene expression in cartilage.

Sheu SY, Ho SR, Sun JS, Chen CY, Ke CJ - BMC Complement Altern Med (2015)

Ecd pre-treatment reduce the catabolic effect of IL-1β on the cartilage explants. Treatment of primary cultures of mouse articular cartilage explants with recombinant mouse IL-1β protein specifically induce the expression of MMP3 (A), MMP13 (B) and ADAMTS-5 (C) genes expression; with the pretreatment of 10−8M Ecd, the catabolic factor genes upregulated by IL-1β treatment are eliminated. (Each value is the mean ± standard deviations; n = 8; *:p<0.05; **:p< 0.01; ***:p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4310028&req=5

Fig3: Ecd pre-treatment reduce the catabolic effect of IL-1β on the cartilage explants. Treatment of primary cultures of mouse articular cartilage explants with recombinant mouse IL-1β protein specifically induce the expression of MMP3 (A), MMP13 (B) and ADAMTS-5 (C) genes expression; with the pretreatment of 10−8M Ecd, the catabolic factor genes upregulated by IL-1β treatment are eliminated. (Each value is the mean ± standard deviations; n = 8; *:p<0.05; **:p< 0.01; ***:p < 0.001).
Mentions: The catabolic effect of IL-1β on cartilage explants are mediated via HIF-2α–induced expression of MMP3, MMP13 and ADAMTS-5. The IL-1β related gene expression of primary mouse articular cartilage explants are examined. Same as noted above, IL-1β enhances Epas1 mRNA expression and suppresses collagen type II (Col2a1) gene expression. With the pretreatment of 10−8M Ecd, it can scavenge IL-1β effect on Epas1 gene expression, but there is also no effect on Col2a1 gene expression (Figure 2). IL-1β treatment also specifically up-regulate MMP3, MMP13 and ADAMTS-5 genes expression (Figure 3). The pre-treatment of 10−8M Ecd can effectively down-regulate the catabolic genes expression. Ecd can reduce the catabolic effect of IL-1β on the cartilage explants; Ecd has protective effects on articular cartilage by inhibiting Epas1, MMP-3, MMP-13 and ADAMTS-5 genes expression.Figure 2

Bottom Line: The effects of Ecd on IL-1β-induced inflammatory conditions and their related catabolic genes expression were analyzed.With the pre-treatment of 10(-8) M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.In conclusions, Ecd can reduce the IL-1β-induced inflammatory effect of the cartilage.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. amel@tmu.edu.tw.

ABSTRACT

Background: In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1β-induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA.

Methods: Chondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2α (EPAS1) in cartilage catabolism simulated by IL-1β (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1β-induced inflammatory conditions and their related catabolic genes expression were analyzed.

Results: Interleukin-1β (IL-1β) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10(-8) M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.

Conclusion: In conclusions, Ecd can reduce the IL-1β-induced inflammatory effect of the cartilage. Ecd may suppress IL-1β-induced cartilage catabolism via HIF-2α pathway.

Show MeSH
Related in: MedlinePlus