Wnt/β-Catenin Signaling Enhances Osteoblastogenic Differentiation from Human Periodontal Ligament Fibroblasts

Heo, Jung Sun; Lee, Seung-Youp; Lee, Jeong-Chae

doi:10.1007/s10059-010-0139-3

Cited by 116 publications

(84 citation statements)

References 36 publications

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“…Our previous study reported that bone-specific transcription factors such as Runx2 and osterix have important roles in LiCl-mediated osteoblastic differentiation (Heo et al, 2010). It is known that osterix acts downstream of Runx2 (Franceschi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Smoothened Leads to Impaired Developments of Postnatal Bone in Mice

Cho

Lim

Hwang

et al. 2012

Molecules and Cells

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Sonic hedgehog (Shh) signaling regulates patterning, proliferation, and stem cell self-renewal in many organs. Smoothened (Smo) plays a key role in transducing Shh signaling into the nucleus by activating a glioma family of transcription factors; however, the cellular and molecular mechanisms underlying the role of sustained Smo activation in postnatal development are still unclear. In this study, we explored the effects of Shh signaling on bone development using a conditional knock-in mouse model that expresses a constitutively activated form of Smo (SmoM2) upon osteocalcin (OCN)-Cre-mediated recombination (SmoM2; OCN-Cre mice). We also evaluated the expression pattern of bone formation-related factors in primary calvarial cultures of mutant and control mice. The SmoM2;OCN-Cre mutant showed growth retardation and reduction of bone mineral density compared to control mice. Constitutively activated SmoM2 also repressed mRNA expression of Runx2, osterix, type I collagen, and osteocalcin. Further, sustained SmoM2 induction suppressed mineralization in calvarial primary osteoblasts cultures, whereas such induction did not affect cell proliferation in the mutant cultures as compared with SmoM2 only control cultures. These results suggest that sustained Smo activation inhibits postnatal development of bone by suppressing gene expression of bone formation regulatory factors in mice.

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Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Smoothened Leads to Impaired Developments of Postnatal Bone in Mice

Cho

Lim

Hwang

et al. 2012

Molecules and Cells

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“…At present, some experimental data have been published regarding the gene expression profile of osteoblastic cell differentiation-related factors using IHC [21][22][23][24][25][26][27][28] , but the examination model is limited to in vitro using cultured cells.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Expression of Osterix Appearing in the Mouse Orthodontic Periodontal Tension Sides

Harada

Nakano

Matsuda

et al. 2012

J. Hard Tissue Biology.

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: Early changes of Osterix expression were examined by immunohistochemistry (IHC) and fluorescent immunohistochemistry (FIHC) in mouse periodontal ligament exposed to experimentally induced orthodontic mechanical stress. Eight-week-old ddY mice were used as experimental animals. To provide continuous orthodontic mechanical stress on the periodontal ligament, a rubber dam sheet was placed between the upper molars of the mice. At 20 min, 1 h, 3 h, 9 h and 24 h after the insertion, related parts of the animal tissues were evaluated by IHC and FIHC regarding Osterix and Runx2 expressions. In the 3-h and 9-h experimental groups, orthodontic tension sites reacted positively. The positive reactions became weak in the experimental group at 24-h. The results suggest that Osterix acts as one of the key factors of osteogenic cell differentiation, which expresses the following after the expression of Runx2, down-steam of Runx2.

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“…In the present work, LEF-1 was found to be one of critical transcription factors for the activity of Crlz1 promoter. As LEF-1 has been reported to be expressed stage-specifically from pro-B to pre-B cells during B cell development (Gutierrez et al, 2010;Reya et al, 2000) and play a role to open its target chromatin with β-catenin in the Wnt (wingless-type MMTV integration site) signaling pathway (Heo et al, 2010;Mosimann et al, 2009), the involvement of LEF-1 in the regulation of Crlz1 promoter activity could provide a potential explanation for the molecular mechanism for the pre-B cell stage-specific activity of Crlz1 promoter, i.e., for the pre-B cell stage-specific histone hyperacetylation and chromatin opening of Crlz1 promoter and thereby its subsequent gene expression (Lim et al, 2006). Therefore, it is possible that the initial binding of pre-B cell stage-specific LEF-1 to the distal region of Crlz1 promoter might open the promoter chromatin to start to activate the promoter specifically in the pre-B cell stage, while multiple bindings of relatively ubiquitous Ets family members such as Fli-1 and GABP to its proximal region might further amplify the Crlz1 promoter activity by multiple additive interactions.…”

Section: Discussionmentioning

confidence: 99%

A Strong Promoter Activity of Pre-B Cell Stage-Specific Crlz1 Gene Is Caused by One Distal LEF-1 and Multiple Proximal Ets Sites

Park

Son

Kang

2011

Molecules and Cells

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The promoter of pre-B cell stage-specific Crlz1 gene, whose protein translocates the cytoplasmic core binding factor β (CBFβ) into the nucleus and thereby allows its heterodimerization with Runx, has a very strong activity, which is about 25% of cytomegalovirus (CMV) promoter activity and comparable to the EF-1α promoter activity. Its transcription start site was mapped at 155 nt upstream of translation initiation codon. 5′-truncation analysis of charged amino acids rich leucine zipper 1 (Crlz1) promoter revealed that one distal region from -612 to -536 and one proximal region from -198 to -100 as numbered from the transcription start site were critical for the promoter activity. The 3′-truncation analysis of the promoter revealed that the basal promoter sequence around the transcription start site, which should be necessary for the assembly of transcription initiation complex and the start of RNA polymerase II, was also essential, although not sufficient by itself. When transcription factor binding sites within those two critical regions were searched by in vivo footprinting, one distal LEF-1 and multiple proximal Ets consensus-like sites were found to be footprinted. Indeed, the protein causing a footprint over the distal region was found to be LEF-1, and the ones causing three footprints over the proximal region were found to be such Ets family members as Fli-1 and GABP, as verified by EMSA and ChIP analyses. Furthermore, those LEF-1 and Ets sites were shown to drive additively a strong transcription of Crlz1 gene.

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Wnt/β-Catenin Signaling Enhances Osteoblastogenic Differentiation from Human Periodontal Ligament Fibroblasts

Cited by 116 publications

References 36 publications

Constitutive Activation of Smoothened Leads to Impaired Developments of Postnatal Bone in Mice

Constitutive Activation of Smoothened Leads to Impaired Developments of Postnatal Bone in Mice

Immunohistochemical Expression of Osterix Appearing in the Mouse Orthodontic Periodontal Tension Sides

A Strong Promoter Activity of Pre-B Cell Stage-Specific Crlz1 Gene Is Caused by One Distal LEF-1 and Multiple Proximal Ets Sites

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