Phytoestrogen (Daidzein) Promotes Chondrogenic Phenotype of Human Chondrocytes in 2D and 3D Culture Systems.

Suhaeb A Mahmod, Simmrat Snigh, Ivan Djordjevic, Yong Mei Yee, Rohana Yusof, Thamil Selvee Ramasamy, Hussin A Rothan
Author Information
  1. Suhaeb A Mahmod: 1Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
  2. Simmrat Snigh: 1Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
  3. Ivan Djordjevic: 2School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798 Singapore.
  4. Yong Mei Yee: 3Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
  5. Rohana Yusof: 3Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
  6. Thamil Selvee Ramasamy: 3Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
  7. Hussin A Rothan: 3Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Abstract

Clinical investigations have shown a significant relationship between osteoarthritis (OA) and estrogens levels in menopausal women. Therefore, treatment with exogenous estrogens has been shown to decrease the risk of OA. However, the effect estrogen has not been clearly demonstrated in the chondrocytes using phytoestrogens, which lack the specific side-effects of estrogens, may provide an alternative therapy. This study was designed to examine the possible effects of phytoestrogen (Daidzein) on Human chondrocyte phenotype and extracellular matrix formation. Phytoestrogens which lack the specific side-effects of estrogens may provide beneficial effect without causing hormone based side effect. Human chondrocytes cells were cultured in 2D (flask) and 3D (PCL-CA scaffold) systems. Daidzein cytotoxic effect was determined by MTT assay. Chondrocyte cellular content of glycosaminoglycans (GAGs), total collagen and chondrogenic gene expression were determined in both culture systems after treatment with Daidzein. Daidzein showed time-dependent and dose-independent effects on chondrocyte bioactivity. The compound at low doses showed significant ( < 0.05) increase in total collagen and GAGs production at similar levels in 2D and 3D culture environment. The mRNA levels of Collagen II and Sox9 were increased significantly ( < 0.01) after the treatment while the upregulation in COMP expression was statistically insignificant ( > 0.05). The expression levels of Fibronectin, Laminin and Integrin β1 were significantly increased especially in 3D culture system. This study was illustrated the potential positive effects of Daidzein on maintenance of Human chondrocyte phenotype and extracellular matrix formation suggesting an attractive and viable alternative therapy for OA.

Keywords

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