title: Cordycepin inhibits chondrocyte hypertrophy of mesenchymal stem cells through PI3K/Bapx1 and Notch signaling pathway.
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 a suitable way to maintain the chondrogenic phenotype of chondrocytes. It has been reported that cordycepin has anti-inflammatory and anti-tumor functions. However, the role of cordycepin in chondrocyte hypertrophy remains unclear. Therefore, the objective of this study was to determine the effect of cordycepin on chondrogenesis and chondrocyte hypertrophy in MSCs and ATDC5 cells. Cordycepin upregulated chondrogenic markers including Sox9 and collagen type II while down-regulated hypertrophic markers including Runx2 and collagen type X. Further exploration showed that cordycepin promoted chondrogenesis through inhibiting Nrf2 while activating BMP signaling. Besides, cordycepin suppressed chondrocyte hypertrophy through PI3K/Bapx1 pathway and Notch signaling. Our results indicated cordycepin had the potential to maintain chondrocyte phenotype and reconstruct engineered cartilage. [BMB Reports 2016; 49(10): 548-553].
authors.affiliation: Department of Anatomy, Third Military Medical University and National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ce
authors.initials: C
authors.lastname: Dou
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Li
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Tang
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Junyu
authors.initials: J
authors.lastname: Xiang
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zhu
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Emergency, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: National & Regional United Engineering Laboratory of Tissue Engineering, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shiwu
authors.initials: S
authors.lastname: Dong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D024043:Collagen Type II / Q000378:metabolism; D024121:Collagen Type X / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D003839:Deoxyadenosines / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D024043:Collagen Type II; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D003839:Deoxyadenosines; D018398:Homeodomain Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C491536:NKX3-2 protein, human; D051880:Receptors, Notch; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; C058120:cordycepin