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

24 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 Institutes of Health/National Institute of Environmental Health Sciences	ZICES043010
National Institutes of Health/National Institute of Environmental Health Sciences
National Institute of Dental and Craniofacial Research	NIDCR R21DE020909
National Institute of Dental and Craniofacial Research

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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.",

author = "Prapaporn Jongwattanapisan and Masahiko Terajima and Miguez, \{Patricia A.\} and William Querido and Hideaki Nagaoka and Noriko Sumida and Gurysh, \{Elizabeth Grace\} and Ainslie, \{Kristy M.\} and Nancy Pleshko and Lalith Perera and Mitsuo Yamauchi",

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AU - Jongwattanapisan, Prapaporn

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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.

AB - 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

Funding

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