title: Cytokine networking of chondrocyte dedifferentiation in vitro and its implications for cell-based cartilage therapy.
abstract: Autologous chondrocyte implantation (ACI) is a golden treatment for large defects of the knee joint without osteoarthritis or other complications. Despite notable progresses, generation of a stable chondrocyte phenotype using progenitor cells remains a main obstacle for chondrocyte-based cartilage treatment. Monolayer chondrocyte expansion in vitro is accompanied by chondrocyte dedifferentiation, which produces a non-specific mechanically inferior extracellular matrix (ECM) unsuitable for ACI. In-depth understanding of the molecular events during chondrocyte dedifferentiation is required to maintain the capacity of in vitro expanded chondrocytes to produce hyaline cartilage-specific ECM. This review discusses key cytokines and signaling pathways involved in chondrocyte dedifferentiation from the standpoint of catabolism and anabolism. Some potential therapeutic strategies are also presented to counteract chondrocyte dedifferentiation for cell-based cartilage therapy.
authors.affiliation: School of Medicine, Sun Yat-sen University Guangzhou 510182, Guangdong Province, China ; Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China ; Department of Orthopedics, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Duan
authors.affiliation: Division of Immunology, University Children's Hospital Zurich Zurich 8032, Switzerland.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: School of Chemical Biology & Biotechnology, Peking University Shenzhen Graduate School Shenzhen 518055, Guangdong Province, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Medicine, Sun Yat-sen University Guangzhou 510182, Guangdong Province, China ; Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China ; Department of Orthopedics, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China.
authors.forename: Jielin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China ; Department of Orthopedics, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Medicine, Sun Yat-sen University Guangzhou 510182, Guangdong Province, China.
authors.forename: Mingtao
authors.initials: M
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Tissue Engineering, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China ; Department of Orthopedics, Shenzhen Second People's Hospital Shenzhen 518035, Guangdong Province, China.
authors.forename: Daping
authors.initials: D
authors.lastname: Wang
keywords: Chondrocyte dedifferentiation; autologous chondrocyte implantation; cartilage repair; cytokines; in vitro; signaling pathways