Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis

P. A. Miguez; M. Terajima; H. Nagaoka; J. A.R. Ferreira; K. Braswell; C. C. Ko; M. Yamauchi

doi:10.1177/0022034514521237

Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis

P. A. Miguez, M. Terajima, H. Nagaoka, J. A.R. Ferreira, K. Braswell, C. C. Ko, M. Yamauchi

Oral Health Science

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

The aim of this study was to determine the effects of glutathione-S- transferase-fused recombinant biglycan (GST-BGN) on craniofacial bone regeneration. We recently demonstrated a positive effect of tissue-derived BGN on bone morphogenetic protein 2 (BMP-2) function, which is exerted likely via the BGN core protein. Here, we investigated the effects of GST-BGN lacking any posttranslational modifications on BMP-2 function in vitro and in vivo. In the C2C12 cell culture system, BMP-2-induced Smad 1/5/8 phosphorylation and alkaline phosphatase activity were both enhanced by the addition of GST-BGN. For the in vivo effect, we employed a Sprague-Dawley rat mandible defect model utilizing 1 μg (optimal) or 0.1 μg (suboptimal) of BMP-2 combined with 0, 2, 4, or 8 μg of GST-BGN. At 2 weeks post-surgery, newly formed bone was evaluated by microcomputed tomography and histologic analyses. The results revealed that the greatest amounts of bone within the defect were formed in the groups of suboptimal BMP-2 combined with 4 or 8 μg of GST-BGN. Also, bone was well organized versus that formed by the optimal dose of BMP. These results indicate that recombinant BGN is an efficient substrate to promote low-dose BMP-induced osteogenesis.

Original language	English
Pages (from-to)	406-411
Number of pages	6
Journal	Journal of Dental Research
Volume	93
Issue number	4
DOIs	https://doi.org/10.1177/0022034514521237
State	Published - Apr 2014

Bibliographical note

Funding Information:
The study was supported in part by the National Institutes of Health (grants R21 DE020909 and AR060978 ).

Keywords

Smad 1/5/8
bone regeneration
critical-sized defect
growth factor
microcomputed tomography
proteoglycan

ASJC Scopus subject areas

General Dentistry

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10.1177/0022034514521237

Cite this

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title = "Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis",

abstract = "The aim of this study was to determine the effects of glutathione-S- transferase-fused recombinant biglycan (GST-BGN) on craniofacial bone regeneration. We recently demonstrated a positive effect of tissue-derived BGN on bone morphogenetic protein 2 (BMP-2) function, which is exerted likely via the BGN core protein. Here, we investigated the effects of GST-BGN lacking any posttranslational modifications on BMP-2 function in vitro and in vivo. In the C2C12 cell culture system, BMP-2-induced Smad 1/5/8 phosphorylation and alkaline phosphatase activity were both enhanced by the addition of GST-BGN. For the in vivo effect, we employed a Sprague-Dawley rat mandible defect model utilizing 1 μg (optimal) or 0.1 μg (suboptimal) of BMP-2 combined with 0, 2, 4, or 8 μg of GST-BGN. At 2 weeks post-surgery, newly formed bone was evaluated by microcomputed tomography and histologic analyses. The results revealed that the greatest amounts of bone within the defect were formed in the groups of suboptimal BMP-2 combined with 4 or 8 μg of GST-BGN. Also, bone was well organized versus that formed by the optimal dose of BMP. These results indicate that recombinant BGN is an efficient substrate to promote low-dose BMP-induced osteogenesis.",

keywords = "Smad 1/5/8, bone regeneration, critical-sized defect, growth factor, microcomputed tomography, proteoglycan",

author = "Miguez, {P. A.} and M. Terajima and H. Nagaoka and Ferreira, {J. A.R.} and K. Braswell and Ko, {C. C.} and M. Yamauchi",

note = "Funding Information: The study was supported in part by the National Institutes of Health (grants R21 DE020909 and AR060978 ). ",

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doi = "10.1177/0022034514521237",

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T1 - Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis

AU - Miguez, P. A.

AU - Terajima, M.

AU - Nagaoka, H.

AU - Ferreira, J. A.R.

AU - Braswell, K.

AU - Ko, C. C.

AU - Yamauchi, M.

N1 - Funding Information: The study was supported in part by the National Institutes of Health (grants R21 DE020909 and AR060978 ).

PY - 2014/4

Y1 - 2014/4

N2 - The aim of this study was to determine the effects of glutathione-S- transferase-fused recombinant biglycan (GST-BGN) on craniofacial bone regeneration. We recently demonstrated a positive effect of tissue-derived BGN on bone morphogenetic protein 2 (BMP-2) function, which is exerted likely via the BGN core protein. Here, we investigated the effects of GST-BGN lacking any posttranslational modifications on BMP-2 function in vitro and in vivo. In the C2C12 cell culture system, BMP-2-induced Smad 1/5/8 phosphorylation and alkaline phosphatase activity were both enhanced by the addition of GST-BGN. For the in vivo effect, we employed a Sprague-Dawley rat mandible defect model utilizing 1 μg (optimal) or 0.1 μg (suboptimal) of BMP-2 combined with 0, 2, 4, or 8 μg of GST-BGN. At 2 weeks post-surgery, newly formed bone was evaluated by microcomputed tomography and histologic analyses. The results revealed that the greatest amounts of bone within the defect were formed in the groups of suboptimal BMP-2 combined with 4 or 8 μg of GST-BGN. Also, bone was well organized versus that formed by the optimal dose of BMP. These results indicate that recombinant BGN is an efficient substrate to promote low-dose BMP-induced osteogenesis.

AB - The aim of this study was to determine the effects of glutathione-S- transferase-fused recombinant biglycan (GST-BGN) on craniofacial bone regeneration. We recently demonstrated a positive effect of tissue-derived BGN on bone morphogenetic protein 2 (BMP-2) function, which is exerted likely via the BGN core protein. Here, we investigated the effects of GST-BGN lacking any posttranslational modifications on BMP-2 function in vitro and in vivo. In the C2C12 cell culture system, BMP-2-induced Smad 1/5/8 phosphorylation and alkaline phosphatase activity were both enhanced by the addition of GST-BGN. For the in vivo effect, we employed a Sprague-Dawley rat mandible defect model utilizing 1 μg (optimal) or 0.1 μg (suboptimal) of BMP-2 combined with 0, 2, 4, or 8 μg of GST-BGN. At 2 weeks post-surgery, newly formed bone was evaluated by microcomputed tomography and histologic analyses. The results revealed that the greatest amounts of bone within the defect were formed in the groups of suboptimal BMP-2 combined with 4 or 8 μg of GST-BGN. Also, bone was well organized versus that formed by the optimal dose of BMP. These results indicate that recombinant BGN is an efficient substrate to promote low-dose BMP-induced osteogenesis.

KW - Smad 1/5/8

KW - bone regeneration

KW - critical-sized defect

KW - growth factor

KW - microcomputed tomography

KW - proteoglycan

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Recombinant biglycan promotes bone morphogenetic protein-induced osteogenesis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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