IMR Press / FBE / Volume 2 / Issue 3 / DOI: 10.2741/E164

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
IkappaBalpha regulates Hes1 in osteoclast differentiation and resorption
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1 Department of Orthodontics, University Medical Centre Groningen, University of Groningen, The Netherlands
2 School of Stomatology, Hainan Medical College, Hainan, China
3 Pathology and Medical Biology, University Medical Centre Groningen, University of Groningen, The Netherlands
4 Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, China
Front. Biosci. (Elite Ed) 2010, 2(3), 1065–1072; https://doi.org/10.2741/E164
Published: 1 June 2010
Abstract

During osteoclast differentiation and resorption, both NF-kappaB and Notch signalling are activated. This study defines the mechanism about the influence of NFkappaB on Notch. To this end, IkappaBalphaM and Wild-type-IkappaBalpha were transfected into RAW 264.7 cells. The number of cells that differentiated into osteoclasts was quantified. The resorption area was measured. NF-kappaB transcriptional activity was determined by EMSA. Hes1, DC-STAMP and MMP-9 mRNA expression levels were determined by RT-PCR. Hes1 protein expression was determined by western blots. ChIP was used to study binding of IkappaBalpha to the Hes1 promoter. NF-kappaB inactivation inhibited the differentiation and resorption ability of osteoclasts. Compared with Wild-type cells, NF-kappaB inactivation resulted in an up-regulation of Hes1 expression, and a down-regulation of DC-STAMP and MMP-9 expression. Moreover, in response to RANKL, NF-kappaB inactivation resulted in a down-regulation of DC-STAMP and MMP-9 expression compared with Wild-type cells. The Hes1 promoter was detected by ChIP using IkappaBalpha antibody. In conclusion, our data suggest IkappaBalpha regulates Hes1-mediated activity in osteoclast differentiation and resorption, which support a cross-talk between NF-kappaB and Notch in osteoclast activity.

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