Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs

Background: Costal chondrocytes (CCs), as a promising donor cell source for cell-based therapy for cartilage repair, have strong tendency of hypertrophy and calcification, which limited CCs from further application in cartilage regenerative medicine. Synovium-derived stromal cells (SDSCs), have show...

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Autores principales:	Yiyang Ma, Kaiwen Zheng, Yidan Pang, Fuzhou Xiang, Junjie Gao, Changqing Zhang, Dajiang Du
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Costal chondrocyte Synovium-derived mesenchymal stromal cell Hypertrophic differentiation Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/0745d7b3be274138a8ee07aa9bcac873
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spelling	oai:doaj.org-article:0745d7b3be274138a8ee07aa9bcac8732021-12-02T05:01:33ZAnti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs2214-031X10.1016/j.jot.2021.05.002https://doaj.org/article/0745d7b3be274138a8ee07aa9bcac8732022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2214031X21000383https://doaj.org/toc/2214-031XBackground: Costal chondrocytes (CCs), as a promising donor cell source for cell-based therapy for cartilage repair, have strong tendency of hypertrophy and calcification, which limited CCs from further application in cartilage regenerative medicine. Synovium-derived stromal cells (SDSCs), have shown their beneficial effect for chondrocytes to maintain phenotype. This study aims to investigate whether SDSCs could help CCs to maintain chondrogenic phenotype and suppress hypertrophic differentiation in cartilage repairs. Methods: CCs were directly cocultured with SDSCs in pellet or indirectly cocultured using a conditioned medium in vitro for 3 weeks. Cartilage matrix formation and hypertrophic differentiation of CCs were analyzed by RT-PCR, biochemical assays, and histological staining. Cocultured pellets were implanted into the osteochondral defects made on the femoral groove of the rats. Then, macroscopic and histological evaluations were performed. Results: Pellets formed by CCs alone and CCs cocultured with SDSCs reveal equal cartilage matrix deposition. However, the gene expression of type X collagen was significantly downregulated in cocultured pellets. Immunohistochemistry analysis revealed suppressed expression of type X collagen in cocultured pellets, indicating SDSCs may suppress hypertrophic differentiation of chondrocytes. Further in indirect coculture experiment, SDSCs suppressed type X collagen expression as well and promoted the proliferation of CCs, indicating SDSCs may influence CCs by paracrine mechanism. The pellets implanted in the osteochondral defects showed good restoration effects, whereas the grafts constructed with CCs and SDSCs showed lower type X expression levels. Conclusion: These results suggest that SDSCs may maintain the phenotype of CCs and prevent the hypertrophic differentiation of CCs in cartilage repair.The Translational Potential of this Article: CCs is a promising donor cell source for cell-based therapy for cartilage repair. Based on our study, cocultured with SDSCs weakened the tendency of hypertrophy and calcification of CCs, which provide a potential usage of SDSCs in CCs-based cartilage repair therapy to suppress newly formed cartilage calcification and improve clinical outcomes.Yiyang MaKaiwen ZhengYidan PangFuzhou XiangJunjie GaoChangqing ZhangDajiang DuElsevierarticleCostal chondrocyteSynovium-derived mesenchymal stromal cellHypertrophic differentiationDiseases of the musculoskeletal systemRC925-935ENJournal of Orthopaedic Translation, Vol 32, Iss , Pp 59-68 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Costal chondrocyte Synovium-derived mesenchymal stromal cell Hypertrophic differentiation Diseases of the musculoskeletal system RC925-935
spellingShingle	Costal chondrocyte Synovium-derived mesenchymal stromal cell Hypertrophic differentiation Diseases of the musculoskeletal system RC925-935 Yiyang Ma Kaiwen Zheng Yidan Pang Fuzhou Xiang Junjie Gao Changqing Zhang Dajiang Du Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
description	Background: Costal chondrocytes (CCs), as a promising donor cell source for cell-based therapy for cartilage repair, have strong tendency of hypertrophy and calcification, which limited CCs from further application in cartilage regenerative medicine. Synovium-derived stromal cells (SDSCs), have shown their beneficial effect for chondrocytes to maintain phenotype. This study aims to investigate whether SDSCs could help CCs to maintain chondrogenic phenotype and suppress hypertrophic differentiation in cartilage repairs. Methods: CCs were directly cocultured with SDSCs in pellet or indirectly cocultured using a conditioned medium in vitro for 3 weeks. Cartilage matrix formation and hypertrophic differentiation of CCs were analyzed by RT-PCR, biochemical assays, and histological staining. Cocultured pellets were implanted into the osteochondral defects made on the femoral groove of the rats. Then, macroscopic and histological evaluations were performed. Results: Pellets formed by CCs alone and CCs cocultured with SDSCs reveal equal cartilage matrix deposition. However, the gene expression of type X collagen was significantly downregulated in cocultured pellets. Immunohistochemistry analysis revealed suppressed expression of type X collagen in cocultured pellets, indicating SDSCs may suppress hypertrophic differentiation of chondrocytes. Further in indirect coculture experiment, SDSCs suppressed type X collagen expression as well and promoted the proliferation of CCs, indicating SDSCs may influence CCs by paracrine mechanism. The pellets implanted in the osteochondral defects showed good restoration effects, whereas the grafts constructed with CCs and SDSCs showed lower type X expression levels. Conclusion: These results suggest that SDSCs may maintain the phenotype of CCs and prevent the hypertrophic differentiation of CCs in cartilage repair.The Translational Potential of this Article: CCs is a promising donor cell source for cell-based therapy for cartilage repair. Based on our study, cocultured with SDSCs weakened the tendency of hypertrophy and calcification of CCs, which provide a potential usage of SDSCs in CCs-based cartilage repair therapy to suppress newly formed cartilage calcification and improve clinical outcomes.
format	article
author	Yiyang Ma Kaiwen Zheng Yidan Pang Fuzhou Xiang Junjie Gao Changqing Zhang Dajiang Du
author_facet	Yiyang Ma Kaiwen Zheng Yidan Pang Fuzhou Xiang Junjie Gao Changqing Zhang Dajiang Du
author_sort	Yiyang Ma
title	Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
title_short	Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
title_full	Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
title_fullStr	Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
title_full_unstemmed	Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
title_sort	anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/0745d7b3be274138a8ee07aa9bcac873
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_version_	1718400751910256640

Anti-hypertrophic effect of synovium-derived stromal cells on costal chondrocytes promotes cartilage repairs

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