title: Synthetic PAMPS gel activates BMP/Smad signaling pathway in ATDC5 cells, which plays a significant role in the gel-induced chondrogenic differentiation.
abstract: The purposes of this study were to identify signaling pathways that were specifically activated in ATDC5 cells cultured on poly (2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel in insulin-free maintenance medium and to evaluate the significance of the determined signaling pathways in the chondrogenic differentiation induced by this gel. In this study, ATDC5 cells cultured on PAMPS gel using the maintenance medium without insulin (PAMPS Culture) were compared with cells cultured on polystyrene using the differentiation medium containing insulin (PS-I Culture). The microarray analysis, Western blot analysis, and real-time PCR analysis demonstrated that the TGF-β/BMP signaling pathway was significantly enhanced at Days 1, 2, and 3 in the PAMPS Culture when compared with the PS-I Culture. Inhibition of the BMP type-I receptor reduced the phosphorylation level of Smad1/5 and expression of type-2 collagen and aggrecan mRNA in the cells accompanied by a reduction in cell aggregation at Day 13 in the PAMPS Culture. The inhibition of the TGF-β/BMP signaling pathway significantly inhibited the chondrogenic differentiation induced by the PAMPS gel. The present study demonstrated that synthetic PAMPS gel activates the TGF-β/BMP/Smad signaling pathway in the ATDC5 cells in the absence of insulin, and that this activation plays a significant role in the chondrogenic differentiation induced by PAMPS gel. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 734-746, 2016.
authors.affiliation: Department of Sports Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Sports Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Department of Sports Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Semba
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohmiya
authors.affiliation: Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Aburatani
authors.affiliation: Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsukura
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Laboratory of Soft and Wet Matter, Department of Advanced Transdisciplinary Sciences, Hokkaido University Faculty of Advanced Life Science, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Laboratory of Soft and Wet Matter, Department of Advanced Transdisciplinary Sciences, Hokkaido University Faculty of Advanced Life Science, Sapporo, Japan.
authors.forename: Jian
authors.initials: J
authors.lastname: Ping Gong
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Sports Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D020219:Chondrogenesis / Q000187:drug effects*; D005782:Gels / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D011137:Polystyrenes / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D013451:Sulfonic Acids / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D005782:Gels; D011108:Polymers; D011137:Polystyrenes; D012333:RNA, Messenger; D051785:Smad Proteins; D013451:Sulfonic Acids; D016212:Transforming Growth Factor beta; C077118:poly(2-acrylamido-2-methyl-1-propanesulfonic acid); D052004:Bone Morphogenetic Protein Receptors
keywords: PAMPS hydrogel; bone morphogenetic protein; chondrogenic differentiation; signaling pathway; transforming growth factor