title: Recombinant human midkine stimulates proliferation and decreases dedifferentiation of auricular chondrocytes in vitro.
abstract: Autologous chondrocyte implantation (ACI) is widely used for the repair of cartilage defects. However, due to the lack of chondrocyte growth factor and dedifferentiation of the cultured primary chondrocytes, cell source has limited the clinical potential of ACI. Auricular cartilage is an attractive potential source of cells for cartilage tissue engineering. Here we demonstrated that recombinant human midkine (rhMK) significantly promoted proliferation of rat primary auricular chondrocytes cultured and passaged in monolayer, which was mediated by the activation of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Furthermore, rhMK attenuated the dedifferentiation of cultured chondrocytes by maintaining the expression of chondrocyte-specific matrix proteins during culture expansion and passage. Importantly, rhMK-expanded chondrocytes reserved their full chondrogenic potential and redifferentiated into elastic chondrocytes after being cultured in high density. The results suggest that rhMK may be used for the preparation of chondrocytes in cartilage tissue engineering.
authors.affiliation: Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai, China.
authors.forename: Chuanying
authors.initials: C
authors.lastname: Xu
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Wu
authors.forename: Shunying
authors.initials: S
authors.lastname: Zhu
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yuan
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D054337:Cell Dedifferentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004425:Ear Cartilage / Q000166:cytology / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D000078792:Midkine; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D000078792:Midkine; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases