Volume 88A, Issue 3 pp. 599-607

Immobilized recombinant human bone morphogenetic protein-2 enhances the phosphorylation of receptor-activated Smads

Eiki Yamachika

Corresponding Author

Eiki Yamachika

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, JapanSearch for more papers by this author
Hidetsugu Tsujigiwa

Hidetsugu Tsujigiwa

Department of Virology, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Nobuaki Shirasu

Nobuaki Shirasu

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Takaaki Ueno

Takaaki Ueno

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Yoshirou Sakata

Yoshirou Sakata

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Joji Fukunaga

Joji Fukunaga

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Nobuyoshi Mizukawa

Nobuyoshi Mizukawa

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Masao Yamada

Masao Yamada

Department of Virology, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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Toshio Sugahara

Toshio Sugahara

Department of Oral and Maxillofacial Reconstructive Surgery, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-Cho, Okayama 700-8525, Japan

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First published: 03 March 2008
Citations: 31

Abstract

Bone morphogenetic protein (BMP)-2 plays an important role in bone growth and regeneration; however, BMP-2 is easily lost by diffusion through body fluid and has some inhibitory pathways. To address this problem, we previously immobilized recombinant human BMP-2 (rhBMP-2) on succinylated type I atelocollagen. Here, we examined the effect of immobilized rhBMP-2 in vitro and vivo. In ST2, MC3T3-E1, and C2C12 cells, alkaline phosphatase activity, which is a marker of osteoblast differentiation, was enhanced more by immobilized than nonimmobilized rhBMP-2. In addition, the phosphorylation of receptor-activated Smads, part of the signaling pathway activated by BMP-2, was prolonged by immobilized rhBMP-2 in these cells. Furthermore, implantation of immobilized rhBMP-2 into the backs of rats promoted the formation of mature bone-like structure. These results demonstrate that immobilized rhBMP-2 has higher bioactivity than nonimmobilized rhBMP-2, and, therefore, immobilization of rhBMP-2 can prolong BMP signaling. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009

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