IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts

R. Clay Bunn; La Tonya D. Green; Michael T. Overgaard; Claus Oxvig; John L. Fowlkes

doi:10.1016/j.bbrc.2004.10.092

IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts

R. Clay Bunn, La Tonya D. Green, Michael T. Overgaard, Claus Oxvig, John L. Fowlkes

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

8 Scopus citations

Abstract

Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzincin pregnancy-associated plasma protein (PAPP)-A. Degradation of IGFBP-4 by PAPP-A or MC3T3-E1 conditioned medium was enhanced by IGF-II but inhibited by mutation of basic residues at or near the PAPP-A cleavage site in IGFBP-4. Furthermore, immunodepletion of PAPP-A from MC3T3-E1 conditioned medium abolished IGFBP-4 degradation. We also found that PAPP-A messenger RNA was expressed throughout differentiation of MC3T3-E1 cells. These results demonstrate for the first time that PAPP-A is the IGFBP-4 protease in MC3T3-E1 cells, a widely used model for osteoblast development, and that PAPP-A may regulate IGF release throughout osteoblast differentiation.

Original language	English
Pages (from-to)	698-706
Number of pages	9
Journal	Biochemical and Biophysical Research Communications
Volume	325
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2004.10.092
State	Published - Dec 17 2004

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant R01DK055653 (J.L.F.), National Institutes of Health Grant C06 RR16517 to Arkansas Children’s Hospital Research Institute and the Arkansas Biosciences Institute (R.C.B. and J.L.F.).

Keywords

Growth factor
IGF
IGFBP
Osteoblast
Protease

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2004.10.092

Cite this

@article{7cb043b7ea7a46d8bb41a5a3075fa02c,

title = "IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts",

abstract = "Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzincin pregnancy-associated plasma protein (PAPP)-A. Degradation of IGFBP-4 by PAPP-A or MC3T3-E1 conditioned medium was enhanced by IGF-II but inhibited by mutation of basic residues at or near the PAPP-A cleavage site in IGFBP-4. Furthermore, immunodepletion of PAPP-A from MC3T3-E1 conditioned medium abolished IGFBP-4 degradation. We also found that PAPP-A messenger RNA was expressed throughout differentiation of MC3T3-E1 cells. These results demonstrate for the first time that PAPP-A is the IGFBP-4 protease in MC3T3-E1 cells, a widely used model for osteoblast development, and that PAPP-A may regulate IGF release throughout osteoblast differentiation.",

keywords = "Growth factor, IGF, IGFBP, Osteoblast, Protease",

author = "Bunn, {R. Clay} and Green, {La Tonya D.} and Overgaard, {Michael T.} and Claus Oxvig and Fowlkes, {John L.}",

note = "Funding Information: This work was supported by National Institutes of Health Grant R01DK055653 (J.L.F.), National Institutes of Health Grant C06 RR16517 to Arkansas Children{\textquoteright}s Hospital Research Institute and the Arkansas Biosciences Institute (R.C.B. and J.L.F.).",

year = "2004",

month = dec,

day = "17",

doi = "10.1016/j.bbrc.2004.10.092",

language = "English",

volume = "325",

pages = "698--706",

number = "3",

}

TY - JOUR

T1 - IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts

AU - Bunn, R. Clay

AU - Green, La Tonya D.

AU - Overgaard, Michael T.

AU - Oxvig, Claus

AU - Fowlkes, John L.

N1 - Funding Information: This work was supported by National Institutes of Health Grant R01DK055653 (J.L.F.), National Institutes of Health Grant C06 RR16517 to Arkansas Children’s Hospital Research Institute and the Arkansas Biosciences Institute (R.C.B. and J.L.F.).

PY - 2004/12/17

Y1 - 2004/12/17

N2 - Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzincin pregnancy-associated plasma protein (PAPP)-A. Degradation of IGFBP-4 by PAPP-A or MC3T3-E1 conditioned medium was enhanced by IGF-II but inhibited by mutation of basic residues at or near the PAPP-A cleavage site in IGFBP-4. Furthermore, immunodepletion of PAPP-A from MC3T3-E1 conditioned medium abolished IGFBP-4 degradation. We also found that PAPP-A messenger RNA was expressed throughout differentiation of MC3T3-E1 cells. These results demonstrate for the first time that PAPP-A is the IGFBP-4 protease in MC3T3-E1 cells, a widely used model for osteoblast development, and that PAPP-A may regulate IGF release throughout osteoblast differentiation.

AB - Insulin-like growth factor (IGF) signaling is critical for osteoblast development and IGF binding protein (IGFBP)-4 is one of the principle IGFBPs expressed by osteoblasts. Release of bound IGF via proteolytic degradation of IGFBP-4 is likely to be critical for osteoblast development. We have investigated whether IGF-sensitive, IGFBP-4 degradation in mouse MC3T3-E1 osteoblasts is due to the metzincin pregnancy-associated plasma protein (PAPP)-A. Degradation of IGFBP-4 by PAPP-A or MC3T3-E1 conditioned medium was enhanced by IGF-II but inhibited by mutation of basic residues at or near the PAPP-A cleavage site in IGFBP-4. Furthermore, immunodepletion of PAPP-A from MC3T3-E1 conditioned medium abolished IGFBP-4 degradation. We also found that PAPP-A messenger RNA was expressed throughout differentiation of MC3T3-E1 cells. These results demonstrate for the first time that PAPP-A is the IGFBP-4 protease in MC3T3-E1 cells, a widely used model for osteoblast development, and that PAPP-A may regulate IGF release throughout osteoblast differentiation.

KW - Growth factor

KW - IGF

KW - IGFBP

KW - Osteoblast

KW - Protease

UR - http://www.scopus.com/inward/record.url?scp=8444238571&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8444238571&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2004.10.092

DO - 10.1016/j.bbrc.2004.10.092

M3 - Article

C2 - 15541345

AN - SCOPUS:8444238571

SN - 0006-291X

VL - 325

SP - 698

EP - 706

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

IGFBP-4 degradation by pregnancy-associated plasma protein-A in MC3T3 osteoblasts

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this