Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function

Prapaporn Jongwattanapisan; Masahiko Terajima; Patricia A. Miguez; William Querido; Hideaki Nagaoka; Noriko Sumida; Elizabeth Grace Gurysh; Kristy M. Ainslie; Nancy Pleshko; Lalith Perera; Mitsuo Yamauchi

doi:10.1038/s41598-018-25279-x

Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function

Prapaporn Jongwattanapisan, Masahiko Terajima, Patricia A. Miguez, William Querido, Hideaki Nagaoka, Noriko Sumida, Elizabeth Grace Gurysh, Kristy M. Ainslie, Nancy Pleshko, Lalith Perera, Mitsuo Yamauchi

Oral Health Science

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

22 Scopus citations

Abstract

We have reported that recombinant biglycan (BGN) core protein accelerates bone formation in vivo by enhancing bone morphogenetic protein (BMP)-2 function. The purpose of the present study was to identify the specific domain ("effector") within the BGN core protein that facilitates BMP-2 osteogenic function. Thus, we generated various recombinant and synthetic peptides corresponding to several domains of BGN, and tested their effects on BMP-2 functions in vitro. The results demonstrated that the leucine-rich repeats 2-3 domain (LRR2-3) of BGN significantly enhanced the BMP-2 induced Smad1/5/9 phosphorylation, osteogenic gene expression, and alkaline phosphatase activity in myogenic C2C12 cells. Furthermore, addition of LRR2-3 to osteoblastic MC3T3-E1 cells accelerated in vitro mineralization without compromising the quality of the mineral and matrix. These data indicate that LRR2-3 is, at least in part, responsible for BGN's ability to enhance BMP-2 osteogenic function, and it could be useful for bone tissue regeneration.

Original language	English
Article number	7022
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-25279-x
State	Published - Dec 1 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

Funding

This work was supported in part by National Institutes of Health grants: NIDCR R21DE020909 (MY), Research Project Z01-ES043010 (to L.P.) in the Intramural Research Program of the NIEHS/NIH, Research Gift Fund (MY).

Funders	Funder number
NIH-NIEHS-SRC
National Institutes of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)	ZICES043010
National Institute of Dental and Craniofacial Research	NIDCR R21DE020909

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title = "Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function",

abstract = "We have reported that recombinant biglycan (BGN) core protein accelerates bone formation in vivo by enhancing bone morphogenetic protein (BMP)-2 function. The purpose of the present study was to identify the specific domain ({"}effector{"}) within the BGN core protein that facilitates BMP-2 osteogenic function. Thus, we generated various recombinant and synthetic peptides corresponding to several domains of BGN, and tested their effects on BMP-2 functions in vitro. The results demonstrated that the leucine-rich repeats 2-3 domain (LRR2-3) of BGN significantly enhanced the BMP-2 induced Smad1/5/9 phosphorylation, osteogenic gene expression, and alkaline phosphatase activity in myogenic C2C12 cells. Furthermore, addition of LRR2-3 to osteoblastic MC3T3-E1 cells accelerated in vitro mineralization without compromising the quality of the mineral and matrix. These data indicate that LRR2-3 is, at least in part, responsible for BGN's ability to enhance BMP-2 osteogenic function, and it could be useful for bone tissue regeneration.",

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AU - Jongwattanapisan, Prapaporn

AU - Terajima, Masahiko

AU - Miguez, Patricia A.

AU - Querido, William

AU - Nagaoka, Hideaki

AU - Sumida, Noriko

AU - Gurysh, Elizabeth Grace

AU - Ainslie, Kristy M.

AU - Pleshko, Nancy

AU - Perera, Lalith

AU - Yamauchi, Mitsuo

PY - 2018/12/1

Y1 - 2018/12/1

N2 - We have reported that recombinant biglycan (BGN) core protein accelerates bone formation in vivo by enhancing bone morphogenetic protein (BMP)-2 function. The purpose of the present study was to identify the specific domain ("effector") within the BGN core protein that facilitates BMP-2 osteogenic function. Thus, we generated various recombinant and synthetic peptides corresponding to several domains of BGN, and tested their effects on BMP-2 functions in vitro. The results demonstrated that the leucine-rich repeats 2-3 domain (LRR2-3) of BGN significantly enhanced the BMP-2 induced Smad1/5/9 phosphorylation, osteogenic gene expression, and alkaline phosphatase activity in myogenic C2C12 cells. Furthermore, addition of LRR2-3 to osteoblastic MC3T3-E1 cells accelerated in vitro mineralization without compromising the quality of the mineral and matrix. These data indicate that LRR2-3 is, at least in part, responsible for BGN's ability to enhance BMP-2 osteogenic function, and it could be useful for bone tissue regeneration.

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Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function

Abstract

Bibliographical note

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