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Stichopus chloronotus aqueous extract as a chondroprotective agent for human chondrocytes isolated from osteoarthitis articular cartilage in vitro


The proinflammatory cytokines, metalloproteinases family (MMPs), inflammatory mediators PGE2, COX-2 and NO are the most important group of compounds responsible for the loss of metabolic homeostasis of articular cartilage by promoting catabolic and destructive processes in the pathogenesis of osteoarthritis (OA). Stichopus chloronotus, a marine sea cucumber which is rich in n-3 PUFAs and phenolic compound, may exert a favorable influence on the course of the disease. The objective of this study was to investigate the regeneration and anti-inflammatory potential of S. chloronotus aqueous extract (SCAE) on human OA articular chondrocytes (HOC). Methods: The HOC isolated from knee joint cartilage removed during surgery were cultured with SCAE for 7 days. The effect of SCAE on anabolic and catabolic gene expression was verified by real-time PCR. Monolayer chondrocytes were stained with toluidine blue whereas sGAG, NO and PGE2 production in medium were analyzed by ELISA. Results: The HOC cultured in various SCAE have polygonal morphology maintaining their chondrocytes characteristic. SAE supplementation tested was found to be effective pro-chondrogenic, anti-inflammatory and anti-oxidative agents, as evidenced by upregulation of cartilage specific markers collagen type II, aggrecan core protein and sox-9 expression and downregulation of collagen type 1, IL-1, IL-6, IL-8, MMP-1, MMP-3, MMP-13, COX-2, iNOS and PAR-2 expression. The presence of SCAE in the culture was able to increase sGAG and reduce NO and PGE2 production significantly. Conclusions: These results suggested that SCAE demonstrated chondroprotective ability by suppressing catabolic activities, oxidative damage and effectively promoting chondrocytes growth.

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We thank the ethical committee for proposal approval and science officers in Tissue Engineering Centre at Universiti Kebangsaan Malaysia Medical Centre for technical assistance and expertise.


This study was made possible with financial support from Universiti Kebangsaan Malaysia (GUP-2013-23) and Ministry of Education Malaysia (ERGS/1/2012/SKK03/UKM/02/1).

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We declare that all authors listed contributed to the acquisition of data, drafting, critical revision and final approval of this manuscripts. Prof. Dr. Ahmad Nazrun Shuid and Dr. Chua Kien Hui conceived of the study and designed research. Dr. Mohd Heikal Mohd Yunus and Dr. Norzana Abd Gafar analyzed data. Dr. Mohd. Heikal Mohd Yunus performed research. Prof. Dr. Ahmad Nazrun Shuid and Dr. Chua Kien Hui helped coordinate the study. Dr. Mohd Heikal bin Mohd Yunus wrote the paper. All authors read and approved the final manuscript. Dr. Mohd Heikal bin Mohd Yunus takes the integrity of this work.

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Correspondence to Mohd Yunus Mohd Heikal.

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Prior ethical approval was obtained from the Research and Ethical Committee of Faculty of Medicine, Universiti Kebangsaan Malaysia (FF-2015-235).

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All the human study subjects provided informed consent.

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Mohd Heikal, M.Y., Ahmad Nazrun, S., Chua, K.H. et al. Stichopus chloronotus aqueous extract as a chondroprotective agent for human chondrocytes isolated from osteoarthitis articular cartilage in vitro. Cytotechnology 71, 521–537 (2019).

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  • Human osteoarthritic articular chondrocytes
  • Stichopus chloronotus
  • Pro-chondrogenic
  • Anti-inflammatory