FGF2 and dexamethasone increase the production of hyaluronan in two-dimensional culture of elastic cartilage-derived cells: in vitro analyses and in vivo cartilage formation |
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Authors: | Akiko Yokoyama Takeshi Muneta Akimoto Nimura Hideyuki Koga Tomoyuki Mochizuki Yuiro Hata Ichiro Sekiya |
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Institution: | (1) Section of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;(2) Department of Plastic and Reconstructive Surgery, Tokyo Medical and Dental University, Tokyo, Japan;(3) Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan;(4) Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan |
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Abstract: | Elastic cartilage-derived cells cultured two-dimensionally with FGF2 and corticosteroid produce gel-type masses that become
mature cartilage when injected into a subcutaneous pocket. This unique method has previously been clinically applied for treatments
of nasal augmentation. However, the components of the gel-type mass and the mechanism of its synthesis remain unknown. Here,
we have investigated the components of the gel-type mass produced by elastic cartilage-derived cells, and whether this gel-type
mass can be produced by using other cell sources or other media. Human elastic cartilage-derived cells from auricular cartilage,
hyaline cartilage-derived cells from articular cartilage, and mesenchymal stem cells from synovium were cultured in three
media: “redifferentiation medium” containing FGF2 and dexamethasone; “chondrogenic medium” containing bone morphogenetic protein-2,
transforming growth factor-β3, and dexamethasone specific for in vitro chondrogenesis of mesenchymal stem cells; control medium.
The elastic cartilage-derived cells cultured in redifferentiation medium produced a gelatinous matrix positive for Alcian
blue. During culture, the amount of chondroitin 4-sulfate, chondroitin 6-sulfate, and especially hyaluronan increased. However,
the expression of RNAs for most chondrogenic genes did not increase. We also reproduced cartilage tissue formation by the
injection of elastic cartilage-derived cells with the gelatinous mass into the subcutaneous space of the nude mouse. The synthesis
of gelatinous matrix in vitro and the formation of cartilage tissue in vivo could be obtained only for the combination of
elastic cartilage-derived cells with redifferentiation medium.
This study was supported in part by grants from the “Japan Society for the Promotion of Science (19591752)” and “Center of
Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone in Tokyo Medical and
Dental University” to Takeshi Muneta, and the “Japan Society for the Promotion of Science (18591657)” to Ichiro Sekiya. |
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Keywords: | Chondrocytes Elastic cartilage Hyaline cartilage Mesenchymal stem cells Hyaluronan Human Mouse (BALB/cAJcl-nu) |
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