title: Characterization of the surface immobilized synthetic heparin binding domain derived from human fibroblast growth factor-2 and its effect on osteoblast differentiation.
abstract: Fibroblast growth factor (FGF)-2 regulates a variety of cellular functions, such as proliferation and differentiation, by binding to cell surface FGF receptors (FGFRs) in the presence of heparin proteoglycans. FGF-2 is known as a heparin-binding growth factor, but the localization of the heparin binding site has not been fully investigated until now. We used two potential heparin binding domains of FGF-2, the residues 105-111 (F105, YKRSRYT) and 119-135 (F119, KRTGQYKLGSKTGPGQK). Peptides could be stably immobilized onto the surface of tissue culture plates. Using solid phase binding assays, we demonstrated that both peptides had higher binding affinity toward heparin compared with nonbinding control sequence. The biological significance of these sites was tested by cell attachment and osteoblast differentiation studies. Cell attachment to the peptides F105 and F119 increased in a dose-dependent manner. Heparin and heparinase treatments decreased cell adhesion to both F105 and F119. This demonstrates that both F105 and F119 interact with cell-surface heparan sulfate proteoglycans, suggesting that FGF-2 has two heparin binding sites. In addition, osteoblast differentiation, confirmed by ALPase activity and mineralization, was increased by surface immobilized peptide F105 and F119. Taken together, these heparin binding peptides could be applied as biological agents enhancing osteoblast differentiation as well as surface modification tools in the tissue regeneration area, especially for bone regeneration.
authors.affiliation: Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.|Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Jue-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.|Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Choo
authors.affiliation: Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.|Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, 17 Haengdang-Dong, Seongdong-Gu, Seoul 133-791, South Korea.
authors.forename: Kuen-Yong
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Geumjeong-Gu, Busan 609-735, South Korea.
authors.forename: Do-Sik
authors.initials: DS
authors.lastname: Min
authors.affiliation: Department of Periodontology, College of Dentistry, WonKwang University, 344-2 Shinyong-Dong, Iksan, Chonbuk 570-749, South Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Pi
authors.affiliation: Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Yang-Jo
authors.initials: YJ
authors.lastname: Seol
authors.affiliation: Department of Pharmacy, College of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, South Korea.
authors.forename: Seung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Center for Biomedical Sciences, Korean National Institute of Health (KNIH), 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea.
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Jo
authors.affiliation: Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.|Department of Periodontology, School of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Chong-Pyoung
authors.initials: CP
authors.lastname: Chung
authors.affiliation: Department of Craniomaxillofacial Reconstructive Science, School of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.|Intellectual Biointerface Engineering Center, College of Dentistry, Seoul National University, 28-22 Yongon-Dong, Chongno-Ku, Seoul 110-749, South Korea.
authors.forename: Yoon-Jeong
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002454:Cell Differentiation; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D000199:Actins; D016222:Fibroblast Growth Factor 2; D006493:Heparin