Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering
Abstract Purpose Chondrocyte -based tissue engineering has been a promising option for the treatment of cartilage lesions. In previous literature, TD198946 has been shown to promote chondrogenic differentiation which could prove useful in cartilage regeneration therapies. Our study aimed to investig...
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doaj-97516ebd8940434dae4b1599a52ce5df2020-11-25T02:10:15ZengSpringerOpenJournal of Experimental Orthopaedics2197-11532020-03-017111410.1186/s40634-020-00228-8Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineeringShuichi Hamamoto0Ryota Chijimatsu1Kazunori Shimomura2Masato Kobayashi3George Jacob4Fumiko Yano5Taku Saito6Ung-il Chung7Sakae Tanaka8Norimasa Nakamura9Orthopaedic Surgery, Osaka University Graduate School of MedicineBone and Cartilage Regenerative Medicine, The University of TokyoOrthopaedic Surgery, Osaka University Graduate School of MedicineOrthopaedic Surgery, Osaka University Graduate School of MedicineOrthopaedic Surgery, Osaka University Graduate School of MedicineBone and Cartilage Regenerative Medicine, The University of TokyoSensory and Motor System Medicine, The University of TokyoCenter for Disease Biology and Integrative Medicine, The University of TokyoSensory and Motor System Medicine, The University of TokyoOrthopaedic Surgery, Osaka University Graduate School of MedicineAbstract Purpose Chondrocyte -based tissue engineering has been a promising option for the treatment of cartilage lesions. In previous literature, TD198946 has been shown to promote chondrogenic differentiation which could prove useful in cartilage regeneration therapies. Our study aimed to investigate the effects of TD198946 in generating engineered cartilage using dedifferentiated chondrocyte-seeded collagen scaffolds treated with TD198946. Methods Articular chondrocytes were isolated from mini pig knees and expanded in 2-dimensional cell culture and subsequently used in the experiments. 3-D pellets were then cultured for two weeks. Cells were also cultured in a type I collagen scaffolds for four weeks. Specimens were cultured with TD198946, BMP-2, or both in combination. Outcomes were determined by gene expression levels of RUNX1, SOX9, ACAN, COL1A1, COL2A1 and COL10A1, the glycosaminoglycan content, and characteristics of histology and immunohistochemistry. Furthermore, the maturity of the engineered cartilage cultured for two weeks was evaluated through subcutaneous implantation in nude mice for four weeks. Results Addition of TD198946 demonstrated the upregulation of gene expression level except for ACAN, type II collagen and glycosaminoglycan synthesis in both pellet and 3D scaffold cultures. TD198946 and BMP-2 combination cultures showed higher chondrogenic differentiation than TD198946 or BMP-2 alone. The engineered cartilage maintained its extracellular matrices for four weeks post implantation. In contrast, engineered cartilage treated with either TD198946 or BMP-2 alone was mostly absorbed. Conclusions Our results indicate that TD198946 could improve quality of engineered cartilage by redifferentiation of dedifferentiated chondrocytes pre-implantation and promoting collagen and glycosaminoglycan synthesis.http://link.springer.com/article/10.1186/s40634-020-00228-8ChondrocytesTD198946ScaffoldEngineered cartilage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuichi Hamamoto Ryota Chijimatsu Kazunori Shimomura Masato Kobayashi George Jacob Fumiko Yano Taku Saito Ung-il Chung Sakae Tanaka Norimasa Nakamura |
spellingShingle |
Shuichi Hamamoto Ryota Chijimatsu Kazunori Shimomura Masato Kobayashi George Jacob Fumiko Yano Taku Saito Ung-il Chung Sakae Tanaka Norimasa Nakamura Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering Journal of Experimental Orthopaedics Chondrocytes TD198946 Scaffold Engineered cartilage |
author_facet |
Shuichi Hamamoto Ryota Chijimatsu Kazunori Shimomura Masato Kobayashi George Jacob Fumiko Yano Taku Saito Ung-il Chung Sakae Tanaka Norimasa Nakamura |
author_sort |
Shuichi Hamamoto |
title |
Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering |
title_short |
Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering |
title_full |
Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering |
title_fullStr |
Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering |
title_full_unstemmed |
Enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering |
title_sort |
enhancement of chondrogenic differentiation supplemented by a novel small compound for chondrocyte-based tissue engineering |
publisher |
SpringerOpen |
series |
Journal of Experimental Orthopaedics |
issn |
2197-1153 |
publishDate |
2020-03-01 |
description |
Abstract Purpose Chondrocyte -based tissue engineering has been a promising option for the treatment of cartilage lesions. In previous literature, TD198946 has been shown to promote chondrogenic differentiation which could prove useful in cartilage regeneration therapies. Our study aimed to investigate the effects of TD198946 in generating engineered cartilage using dedifferentiated chondrocyte-seeded collagen scaffolds treated with TD198946. Methods Articular chondrocytes were isolated from mini pig knees and expanded in 2-dimensional cell culture and subsequently used in the experiments. 3-D pellets were then cultured for two weeks. Cells were also cultured in a type I collagen scaffolds for four weeks. Specimens were cultured with TD198946, BMP-2, or both in combination. Outcomes were determined by gene expression levels of RUNX1, SOX9, ACAN, COL1A1, COL2A1 and COL10A1, the glycosaminoglycan content, and characteristics of histology and immunohistochemistry. Furthermore, the maturity of the engineered cartilage cultured for two weeks was evaluated through subcutaneous implantation in nude mice for four weeks. Results Addition of TD198946 demonstrated the upregulation of gene expression level except for ACAN, type II collagen and glycosaminoglycan synthesis in both pellet and 3D scaffold cultures. TD198946 and BMP-2 combination cultures showed higher chondrogenic differentiation than TD198946 or BMP-2 alone. The engineered cartilage maintained its extracellular matrices for four weeks post implantation. In contrast, engineered cartilage treated with either TD198946 or BMP-2 alone was mostly absorbed. Conclusions Our results indicate that TD198946 could improve quality of engineered cartilage by redifferentiation of dedifferentiated chondrocytes pre-implantation and promoting collagen and glycosaminoglycan synthesis. |
topic |
Chondrocytes TD198946 Scaffold Engineered cartilage |
url |
http://link.springer.com/article/10.1186/s40634-020-00228-8 |
work_keys_str_mv |
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