Inhibition of bone morphogenetic protein-induced osteoblast differentiation

Shoichiro Kokabu, Shizu Tsuchiya-Hirata, Hidefumi Fukushima, Goro Sugiyama, Jonathan W. Lowery, Takenobu Katagiri, Eijiro Jimi

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

Background Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo and osteoblast differentiation of various cells in vitro. Therefore, BMPs are thought to be useful in bone regeneration medicine and for treating bone-related diseases. However, clinical application of BMPs is not widespread. Highlight BMP signal transduction and BMP-induced osteoblast differentiation are negatively regulated at several steps. BMP-3 acts as an antagonist to activin receptor type 2B and suppresses osteoblast differentiation of bone marrow stromal cells (BMSCs). Targeted disruption of Bmp-3 in mice increases trabecular bone formation and bone mass. A selective inhibitor of classical NF-κB pathway enhances BMP-2-induced ectopic bone formation in vivo. NF-κB inhibits BMP-induced osteoblast differentiation by directly targeting SMAD proteins. p65, the main subunit of NF-κB, interacts with SMAD4 and interferes with the DNA binding of SMAD complex, thus suppressing BMP-induced osteoblast differentiation. Transducin-like enhancer of split 3 (TLE3), a member of Groucho/TLE family, represses the transactivation of RUNX2, one of the master regulators of osteoblast differentiation, thus suppressing BMP-induced osteoblast differentiation of BMSCs. Conclusion In addition to BMP-3, NF-κB, and TLE3, numerous inhibitors suppress BMP-induced osteoblast differentiation. Therefore, a precise understanding of mechanisms underlying the inhibition of osteoblast differentiation may help develop novel methods for treating bone-related diseases or for the tissue engineering of the bone.

Original languageEnglish
Pages (from-to)179-184
Number of pages6
Journaljournal of oral biosciences
Volume57
Issue number4
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Fingerprint

Bone Morphogenetic Proteins
Osteoblasts
Bone
Bone Morphogenetic Protein 3
Osteogenesis
Transducin
Bone Diseases
Mesenchymal Stromal Cells
Activin Receptors
Bone and Bones
Bone Morphogenetic Protein 2
Bone Regeneration
Signal transduction
Protein Transport
Tissue Engineering
Transcriptional Activation
Tissue engineering
Cell Differentiation
Signal Transduction
Medicine

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Dentistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Inhibition of bone morphogenetic protein-induced osteoblast differentiation. / Kokabu, Shoichiro; Tsuchiya-Hirata, Shizu; Fukushima, Hidefumi; Sugiyama, Goro; Lowery, Jonathan W.; Katagiri, Takenobu; Jimi, Eijiro.

In: journal of oral biosciences, Vol. 57, No. 4, 01.01.2015, p. 179-184.

Research output: Contribution to journalReview article

Kokabu, Shoichiro ; Tsuchiya-Hirata, Shizu ; Fukushima, Hidefumi ; Sugiyama, Goro ; Lowery, Jonathan W. ; Katagiri, Takenobu ; Jimi, Eijiro. / Inhibition of bone morphogenetic protein-induced osteoblast differentiation. In: journal of oral biosciences. 2015 ; Vol. 57, No. 4. pp. 179-184.
@article{8d48122c462b4a8c928d05675f2b1385,
title = "Inhibition of bone morphogenetic protein-induced osteoblast differentiation",
abstract = "Background Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo and osteoblast differentiation of various cells in vitro. Therefore, BMPs are thought to be useful in bone regeneration medicine and for treating bone-related diseases. However, clinical application of BMPs is not widespread. Highlight BMP signal transduction and BMP-induced osteoblast differentiation are negatively regulated at several steps. BMP-3 acts as an antagonist to activin receptor type 2B and suppresses osteoblast differentiation of bone marrow stromal cells (BMSCs). Targeted disruption of Bmp-3 in mice increases trabecular bone formation and bone mass. A selective inhibitor of classical NF-κB pathway enhances BMP-2-induced ectopic bone formation in vivo. NF-κB inhibits BMP-induced osteoblast differentiation by directly targeting SMAD proteins. p65, the main subunit of NF-κB, interacts with SMAD4 and interferes with the DNA binding of SMAD complex, thus suppressing BMP-induced osteoblast differentiation. Transducin-like enhancer of split 3 (TLE3), a member of Groucho/TLE family, represses the transactivation of RUNX2, one of the master regulators of osteoblast differentiation, thus suppressing BMP-induced osteoblast differentiation of BMSCs. Conclusion In addition to BMP-3, NF-κB, and TLE3, numerous inhibitors suppress BMP-induced osteoblast differentiation. Therefore, a precise understanding of mechanisms underlying the inhibition of osteoblast differentiation may help develop novel methods for treating bone-related diseases or for the tissue engineering of the bone.",
author = "Shoichiro Kokabu and Shizu Tsuchiya-Hirata and Hidefumi Fukushima and Goro Sugiyama and Lowery, {Jonathan W.} and Takenobu Katagiri and Eijiro Jimi",
year = "2015",
month = "1",
day = "1",
doi = "10.1016/j.job.2015.05.005",
language = "English",
volume = "57",
pages = "179--184",
journal = "Journal of Oral Biosciences",
issn = "1349-0079",
publisher = "Japanese Association for Oral Biology",
number = "4",

}

TY - JOUR

T1 - Inhibition of bone morphogenetic protein-induced osteoblast differentiation

AU - Kokabu, Shoichiro

AU - Tsuchiya-Hirata, Shizu

AU - Fukushima, Hidefumi

AU - Sugiyama, Goro

AU - Lowery, Jonathan W.

AU - Katagiri, Takenobu

AU - Jimi, Eijiro

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo and osteoblast differentiation of various cells in vitro. Therefore, BMPs are thought to be useful in bone regeneration medicine and for treating bone-related diseases. However, clinical application of BMPs is not widespread. Highlight BMP signal transduction and BMP-induced osteoblast differentiation are negatively regulated at several steps. BMP-3 acts as an antagonist to activin receptor type 2B and suppresses osteoblast differentiation of bone marrow stromal cells (BMSCs). Targeted disruption of Bmp-3 in mice increases trabecular bone formation and bone mass. A selective inhibitor of classical NF-κB pathway enhances BMP-2-induced ectopic bone formation in vivo. NF-κB inhibits BMP-induced osteoblast differentiation by directly targeting SMAD proteins. p65, the main subunit of NF-κB, interacts with SMAD4 and interferes with the DNA binding of SMAD complex, thus suppressing BMP-induced osteoblast differentiation. Transducin-like enhancer of split 3 (TLE3), a member of Groucho/TLE family, represses the transactivation of RUNX2, one of the master regulators of osteoblast differentiation, thus suppressing BMP-induced osteoblast differentiation of BMSCs. Conclusion In addition to BMP-3, NF-κB, and TLE3, numerous inhibitors suppress BMP-induced osteoblast differentiation. Therefore, a precise understanding of mechanisms underlying the inhibition of osteoblast differentiation may help develop novel methods for treating bone-related diseases or for the tissue engineering of the bone.

AB - Background Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo and osteoblast differentiation of various cells in vitro. Therefore, BMPs are thought to be useful in bone regeneration medicine and for treating bone-related diseases. However, clinical application of BMPs is not widespread. Highlight BMP signal transduction and BMP-induced osteoblast differentiation are negatively regulated at several steps. BMP-3 acts as an antagonist to activin receptor type 2B and suppresses osteoblast differentiation of bone marrow stromal cells (BMSCs). Targeted disruption of Bmp-3 in mice increases trabecular bone formation and bone mass. A selective inhibitor of classical NF-κB pathway enhances BMP-2-induced ectopic bone formation in vivo. NF-κB inhibits BMP-induced osteoblast differentiation by directly targeting SMAD proteins. p65, the main subunit of NF-κB, interacts with SMAD4 and interferes with the DNA binding of SMAD complex, thus suppressing BMP-induced osteoblast differentiation. Transducin-like enhancer of split 3 (TLE3), a member of Groucho/TLE family, represses the transactivation of RUNX2, one of the master regulators of osteoblast differentiation, thus suppressing BMP-induced osteoblast differentiation of BMSCs. Conclusion In addition to BMP-3, NF-κB, and TLE3, numerous inhibitors suppress BMP-induced osteoblast differentiation. Therefore, a precise understanding of mechanisms underlying the inhibition of osteoblast differentiation may help develop novel methods for treating bone-related diseases or for the tissue engineering of the bone.

UR - http://www.scopus.com/inward/record.url?scp=84952631186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952631186&partnerID=8YFLogxK

U2 - 10.1016/j.job.2015.05.005

DO - 10.1016/j.job.2015.05.005

M3 - Review article

AN - SCOPUS:84952631186

VL - 57

SP - 179

EP - 184

JO - Journal of Oral Biosciences

JF - Journal of Oral Biosciences

SN - 1349-0079

IS - 4

ER -