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Published in: Arthritis Research & Therapy 4/2008

01-08-2008 | Editorial

Suppression of bone morphogenetic protein inhibitors promotes osteogenic differentiation: therapeutic implications

Authors: Manolis Heliotis, Eleftherios Tsiridis

Published in: Arthritis Research & Therapy | Issue 4/2008

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Abstract

Bone morphogenetic proteins (BMPs) are expressed during osteogenesis and their action is regulated by corresponding BMP inhibitors. Chordin (a well recognized BMP inhibitor) and BMP-2 are expressed during osteogenic differentiation of human mesenchymal stem cells. Chordin inhibition induces human mesenchymal stem cell differentiation and reduces their proliferation by increasing BMP-2 bioavailability. The potential of suppressing BMP inhibitors is emerging as a biological therapeutic target in bone tissue engineering, because it results in an unopposed synergy between the various growth factors that are involved in osteogenesis, within their physiological milieu.
Literature
1.
go back to reference Kwong FNK, Richardson SM, Evans CH: Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. Arthritis Res Ther. 2008, 10: R65-10.1186/ar2436.PubMedCentralCrossRefPubMed Kwong FNK, Richardson SM, Evans CH: Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. Arthritis Res Ther. 2008, 10: R65-10.1186/ar2436.PubMedCentralCrossRefPubMed
2.
go back to reference Cho TJ, Gerstenfeld LC, Einhorn TA: Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res. 2002, 17: 513-520. 10.1359/jbmr.2002.17.3.513.CrossRefPubMed Cho TJ, Gerstenfeld LC, Einhorn TA: Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res. 2002, 17: 513-520. 10.1359/jbmr.2002.17.3.513.CrossRefPubMed
3.
go back to reference Sakou T, Onishi T, Yamamoto T, Nagamine T, Sampath T, Ten Dijke P: Localization of Smads, the TGF-beta family intracellular signaling components during endochondral ossification. J Bone Miner Res. 1999, 14: 1145-1152. 10.1359/jbmr.1999.14.7.1145.CrossRefPubMed Sakou T, Onishi T, Yamamoto T, Nagamine T, Sampath T, Ten Dijke P: Localization of Smads, the TGF-beta family intracellular signaling components during endochondral ossification. J Bone Miner Res. 1999, 14: 1145-1152. 10.1359/jbmr.1999.14.7.1145.CrossRefPubMed
4.
go back to reference Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S: Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature. 2002, 420: 636-642. 10.1038/nature01245.CrossRefPubMed Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S: Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature. 2002, 420: 636-642. 10.1038/nature01245.CrossRefPubMed
5.
go back to reference Chang C, Holtzman DA, Chau S, Chickering T, Woolf EA, Holmgren LM, Bodorova J, Gearing DP, Holmes WE, Brivanlou AH: Twisted gastrulation can function as a BMP antagonist. Nature. 2001, 410: 483-487. 10.1038/35068583.CrossRefPubMed Chang C, Holtzman DA, Chau S, Chickering T, Woolf EA, Holmgren LM, Bodorova J, Gearing DP, Holmes WE, Brivanlou AH: Twisted gastrulation can function as a BMP antagonist. Nature. 2001, 410: 483-487. 10.1038/35068583.CrossRefPubMed
6.
go back to reference Gazzerro E, Pereira RC, Jorgetti V, Olson S, Economides AN, Canalis E: Skeletal overexpression of gremlin impairs bone formation and causes osteopenia. Endocrinology. 2005, 146: 655-665. 10.1210/en.2004-0766.CrossRefPubMed Gazzerro E, Pereira RC, Jorgetti V, Olson S, Economides AN, Canalis E: Skeletal overexpression of gremlin impairs bone formation and causes osteopenia. Endocrinology. 2005, 146: 655-665. 10.1210/en.2004-0766.CrossRefPubMed
7.
go back to reference Winkler DG, Yu C, Geoghegan JC, Ojala EW, Skonier JE, Shpektor D, Sutherland MK, Latham JA: Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex. J Biol Chem. 2004, 279: 36293-36298. 10.1074/jbc.M400521200.CrossRefPubMed Winkler DG, Yu C, Geoghegan JC, Ojala EW, Skonier JE, Shpektor D, Sutherland MK, Latham JA: Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex. J Biol Chem. 2004, 279: 36293-36298. 10.1074/jbc.M400521200.CrossRefPubMed
8.
go back to reference Wan DC, Pomerantz JH, Brunet LJ, Kim JB, Chou YF, Wu BM, Harland R, Blau HM, Longaker MT: Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. J Biol Chem. 2007, 282: 26450-26459. 10.1074/jbc.M703282200.CrossRefPubMed Wan DC, Pomerantz JH, Brunet LJ, Kim JB, Chou YF, Wu BM, Harland R, Blau HM, Longaker MT: Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. J Biol Chem. 2007, 282: 26450-26459. 10.1074/jbc.M703282200.CrossRefPubMed
9.
go back to reference Tsiridis E, Ali Z, Bhalla A, Heliotis M, Gurav N, Deb S, DiSilvio L: In vitro and in vivo optimization of impaction allografting by demineralization and addition of rh-OP-1. J Orthop Res. 2007, 25: 1425-1437. 10.1002/jor.20387.CrossRefPubMed Tsiridis E, Ali Z, Bhalla A, Heliotis M, Gurav N, Deb S, DiSilvio L: In vitro and in vivo optimization of impaction allografting by demineralization and addition of rh-OP-1. J Orthop Res. 2007, 25: 1425-1437. 10.1002/jor.20387.CrossRefPubMed
10.
go back to reference Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E: Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest. 2003, 112: 924-934.PubMedCentralCrossRefPubMed Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E: Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest. 2003, 112: 924-934.PubMedCentralCrossRefPubMed
Metadata
Title
Suppression of bone morphogenetic protein inhibitors promotes osteogenic differentiation: therapeutic implications
Authors
Manolis Heliotis
Eleftherios Tsiridis
Publication date
01-08-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2467

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