title: Effect of FGF-2 on collagen tissue regeneration by human vertebral bone marrow stem cells.
abstract: The effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human bone marrow stem cells (hBMSCs) were investigated. hBMSCs were isolated from human vertebral body bone marrow during vertebral surgery and a population of hBMSCs with the characteristics of mesenchymal stem cells was observed. The FGF-2 treatment (5 ng/mL) affected on the colony-forming efficiency, proliferation, and in vitro differentiation of hBMSCs. Insoluble/soluble collagen and hydroxyproline synthesis was significantly enhanced in hBMSCs expanded with FGF-2 and the treatment of FGF-2 caused a reduction in the mRNA expression of collagen type I, but an increase of collagen types II and III along with lysyl oxidase family genes. Collagen formation was also examined using an in vivo assay model by transplanting hBMSCs into immunocompromised mice (n=4) and the histologic and immunohistochemical results revealed that significantly more collagen with a well-organized structure was formed by FGF-2-treated hBMSCs at 8 weeks posttransplantation (P<0.05). The DNA microarray assay demonstrated that genes related to extracellular matrix formation were significantly upregulated. To elucidate the underlying mechanism, chemical inhibitors against extracellular-signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) were treated and following downstream expression was observed. Collectively, FGF-2 facilitated the collagen-producing potency of hBMSCs both in vitro and in vivo, rendering them more suitable for use in collagen regeneration in the clinical field.
authors.affiliation: 1 Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University , Seoul, Korea.
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Park
authors.forename: Jung-Chul
authors.initials: JC
authors.lastname: Park
authors.forename: Jung-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Tae-Wan
authors.initials: TW
authors.lastname: Kim
authors.forename: Ki-Joon
authors.initials: KJ
authors.lastname: Kim
authors.forename: Byung-Joo
authors.initials: BJ
authors.lastname: Jung
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Shim
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Choi
authors.forename: So-Yon
authors.initials: SY
authors.lastname: Park
authors.forename: Kyoo-Sung
authors.initials: KS
authors.lastname: Cho
authors.forename: Chang-Sung
authors.initials: CS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects*; D013131:Spine / Q000166:cytology / Q000378:metabolism*
chemical_list: D016222:Fibroblast Growth Factor 2; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase