2012 Fiscal Year Final Research Report
Enhancement of the BMP-induced bone formation by the inhibition of NF-κB based on genetic evidence
| Project/Area Number |
22592042
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
ZHANG Min 九州歯科大学, 歯学部, 助教 (00326472)
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| Co-Investigator(Kenkyū-buntansha) |
KOU Matsuo 九州歯科大学, 歯学部, 准教授 (70238971)
JIMI Eijiro 九州歯科大学, 歯学部, 教授 (40276598)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 骨再生 / NF-κB / 骨芽細胞 / BMP / 骨代謝 |
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| Research Abstract |
We previously reported that alymphoplasia (aly/aly) mice, which have a natural loss-of-function mutation in the Nik gene, which encodes a kinase essential for the processing of p100 to p52 in the alternative nuclear factor-κB (NF-κB) pathway, show mild osteopetrosis with an increase in several parameters of bone formation: bone formation rate, mineral apposition rate, and osteoblast number. We therefore investigated the molecular mechanisms triggered by the alternative NF-κB pathway in the regulation of osteoblast differentiation using primary osteoblasts (POB) prepared from aly/aly mice. Alkaline phosphatase (ALP) activity and mineralization induced by the presence of β-glycerophosphate and ascorbic acid were enhanced in POB from aly/aly compared with wild-type (WT) mice. Furthermore, osteoblastic differentiation induced by bone morphogenetic protein 2 (BMP2), as shown by ALP activity, mRNA expression of osteocalcin, Id1, Osterix and Runx2, and Sma- and Mad-related protein (Smad)1/5/8 phosphorylation, was also enhanced in POB from aly/aly mice. The ectopic bone formation in vivo that was induced by BMP2 was enhanced in aly/aly mice compared with controls. Transfection of a mutant form of p100, p100ΔGRR, which cannot be processed to p52, stimulated ALP activity and Smad phosphorylation. In contrast to p100ΔGRR, overexpression of p52 inhibited these events. Both BMP2-induced ALP activity and Smad phosphorylation were reduced in POB from p100-deficient mice, which carry a homozygous deletion of the COOH-terminal ankyrin repeats of p100 but still express functional p52 protein. p52 and p100ΔGRR interacted with a BMP receptor, ALK2, in overexpressed COS7 cells and changed the ALK2 protein levels in opposite directions: p52 reduced ALK2 and p100 increased it. Thus, the alternative the NF-κB pathway via the processing of p52 from p100 negatively regulates osteoblastic differentiation and bone formation by modifying BMP activity.
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Research Products
(23 results)
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[Journal Article] Magnetic resonance angiography with fresh blood imaging for identication of hemangiomas and blood vessels around hemangiomas in oral and maxillofacial regions2012
Author(s)
MOda,T Tanaka, SKito,S Matsumoto-Takeda, K Otsuka, Y Hayashi, N Wakasugi-Sato,I Yoshioka,M Habu, S Kokuryo,M Kodama,S Nogami, I Miyamoto, N Yamamoto, A Ishikawa, M Zhang,K Matsuo, S Shiiba, Y Seta, Y Yamashita,TTakahashi,KTominaga,Ymorimoto
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Journal Title
Oral Surg Oral Med Oral Pathol Oral Radiol
Volume: 113(4)
Pages: 559-566
DOI
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[Journal Article] Accumulation of p100, a precursor of NF-κB2011
Author(s)
SeoY, Fukushima H, Maruyama T, Nakao Kuroishi K, Osawa K, Nagano K, Aoki K, Weih F, Doi T, Zhang M, Ohya K, Katagiri T, Hosokawa R, Jimi E.
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Journal Title
enhances osteoblastic differentiation in vitroand bone formation in vivoin aly/alymice Mol Endocrinol
Volume: 26
Pages: 414-422
DOI
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[Journal Article] Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation.2011
Author(s)
Tsutsumi K, Matsuda M, Kotani M, Mizokami A, Murakami A, Takahashi I, Terada Y, Kanematsu T, Fukami K, Takenawa T, Jimi E, Hirata M
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Journal Title
J Biol Chem
Volume: 286
Pages: 31032-31042
DOI
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