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Cordycepin inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through PI3K/Bapx1 and Notch Signaling Pathway
Zhen Cao1,2, Ce Dou2, Jianmei Li2, Xiangyu Tang2, Junyu Xiang2, Chunrong Zhao2, Lingyu Zhu2, Yun Bai2, Qiang Xiang3, Shiwu Dong2,*
1Department of Anatomy, Third Military Medical University,
2Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University,
3Department of Emergency, Southwest Hospital, Third Military Medical University
Abstract
Mesenchymal stem cells (MSCs) are widely used in cartilage tissue engineering to repair articular cartilage defects. However, hypertrophy of chondrocytes derived from MSCs might hinder the stabilization of hyaline cartilage. Thus, it is very important to find out a suitable way to maintain the chondrogenic phenotype of chondrocytes. Cordycepin was reported with anti-inflammatory and anti-tumor functions. However, the role of cordycepin in the chondrocyte hypertrophy remains unclear. We investigated the effect of cordycepin on chondrogenesis and chondrocyte hypertrophy in MSCs and ATDC5 cells. Cordycepin up-regulated chondrogenic markers including Sox9 and collagen type ケ while down-regulated hypertrophic markers including Runx2 and collagen type ス. Further exploration showed that cordycepin promoted chondrogenesis through inhibiting Nrft and activating BMP signaling. Besides, cordycepin suppressed chondrocyte hypertrophy through PI3K/Bapx1 pathway and Notch signaling. Our results indicated cordycepin was a potential agent in maintaining chondrocyte phenotype and reconstructing engineered cartilage.
Abstract, Accepted Manuscript(in press) [Submitted on April 20, 2016, Accepted on July 15, 2016]
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