title: Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling.
abstract: The hydrophobic (HPB) nature of most polymeric biomaterials has been a major obstacle in using those materials in vivo due to low compatibility with cells. However, there is little knowledge of the molecular detail to explain how surface hydrophobicity affects cell responses. In this study, we compared the proliferation and apoptosis of human osteoblastic MG63 cells adhered to hydrophilic (HPL) and hydrophobic surfaces. On the hydrophobic surface, less formation of focal contacts and actin stress fibers, a delay in cell cycle progression, and an increase in apoptosis were observed. By using fibroblast growth factor 1 (FGF1) as a model growth factor, we also investigated intracellular signaling pathways on hydrophilic and hydrophobic surfaces. The activation of Ras, Akt, and ERK by FGF1 was impaired in MG63 cells on the hydrophobic surface. The overexpression of constitutively active form of Ras and Akt rescued those cells from apoptosis and recovered cell cycle progression. Furthermore, their overexpression also restored the actin cytoskeletal organization on the hydrophobic surface. Finally, the proliferative, antiapoptotic, and cytoskeletal effects of constitutively active Ras in MG63 cells on the hydrophobic surface were blocked by wortmannin and PD98059 that inhibit Akt and ERK activation, respectively. Therefore, our results suggest that the activation of Ras and its downstream molecules Akt and ERK to an appropriate level is one of crucial elements in the determination of osteoblast cell responses. The Ras pathway may represent a cell biological target that should be considered for successful surface modification of biomaterials to induce adequate cell responses in the bone tissue.
authors.affiliation: Laboratory for the Study of Molecular Biointerfaces, Department of CMF Cell and Developmental Biology, College of Dentistry and DRI, and Intellectual Biointerface Engineering Center, Seoul National University, Seoul 110-749, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Huh
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Kim
authors.forename: Jea
authors.initials: J
authors.lastname: Seung Ko
authors.forename: Chong-Pyoung
authors.initials: CP
authors.lastname: Chung
authors.forename: Hyun-Man
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D022001:Focal Adhesions / Q000378:metabolism*; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010006:Osteoblasts / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology*; D022502:Stress Fibers / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D005419:Flavonoids; D011518:Proto-Oncogene Proteins; D016220:Fibroblast Growth Factor 1; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin