Type II collagen and glycosaminoglycan expression induction in primary human chondrocyte by TGF-β1
| Autor: | Youngsuk Yi, Hyun Joo Yoon, Dhara Somaiya, Yeon-Ju Lee, Chae-Lyul Lim, Choi Kyoungbaek, Kwan Hee Lee, Suk Bum Kim, Hyeon-Youl Lee, Moon Jong Noh |
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| Rok vydání: | 2015 |
| Předmět: |
Cartilage
Articular Type II collagen Transfection Chondrocyte Transforming Growth Factor beta1 Glycosaminoglycan Chondrocytes Rheumatology Chlorocebus aethiops Cell Adhesion medicine Animals Humans Regeneration Orthopedics and Sports Medicine Femur Cell adhesion Collagen Type II Glycosaminoglycans biology business.industry Cartilage Infant Genetic Therapy Hep G2 Cells Chondrogenesis Coculture Techniques Up-Regulation Cell biology Disease Models Animal medicine.anatomical_structure Proteoglycan COS Cells Mutation Immunology biology.protein Rabbits business Cartilage Diseases Research Article |
| Zdroj: | BMC Musculoskeletal Disorders |
| ISSN: | 1471-2474 |
| DOI: | 10.1186/s12891-015-0599-x |
| Popis: | Background A localized non-surgical delivery of allogeneic human chondrocytes (hChonJ) with irradiated genetically modified chondrocytes (hChonJb#7) expressing transforming growth factor-β1 (TGF-β1) showed efficacy in regenerating cartilage tissue in our pre-clinical studies and human Phase I and II clinical trials. These previous observations led us to investigate the molecular mechanisms of the cartilage regeneration. Methods Genetically modified TGF-β1preprotein was evaluated by monitoring cell proliferation inhibition activity. The effect of modified TGF-β1 on chondrocytes was evaluated based on the type II collagen mRNA levels and the amount of glycosaminoclycan (GAG) formed around chondrocytes, which are indicative markers of redifferentiated chondrocytes. Among the cartilage matrix components produced by hChonJb#7 cells, type II collagen and proteoglycan, in addition to TGF-β1, were also tested to see if they could induce hChonJ redifferentiation. The ability of chondrocytes to attach to artificially induced defects in rabbit cartilage was tested using fluorescent markers. Results Throughout these experiments, the TGF-β1 produced from hChonJb#7 was shown to be equally as active as the recombinant human TGF-β1. Type II collagen and GAG production were induced in hChonJ cells by TGF-β1 secreted from the irradiated hChonJb#7 cells when the cells were co-cultured in micro-masses. Both hChonJ and hChonJb#7 cells could attach efficiently to the defect area in the rabbit cartilage. Conclusions This study suggests that the mixture (TG-C) of allogeneic human chondrocytes (hChonJ) and irradiated genetically modified human chondrocytes expressing TGF-β1 (hChonJb#7) attach to the damaged cartilage area to produce type II collagen-GAG matrices by providing a continuous supply of active TGF-β1. |
| Databáze: | OpenAIRE |
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