Abstract
CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100 ng/μl was able to induce strong CCN2 expression while a minimum concentration of 25 ng/μl was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme.
| Original language | English |
|---|---|
| Pages (from-to) | 1659-1666 |
| Number of pages | 8 |
| Journal | Archives of Oral Biology |
| Volume | 58 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2013 |
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Keywords
- BMP
- CCN
- CCN2
- FGF
- Tooth development
ASJC Scopus subject areas
- Otorhinolaryngology
- Cell Biology
- Dentistry(all)
Cite this
Regulation of CCN2 gene expression and possible roles in developing tooth germs. / Kanyama, Manabu; Shimo, Tsuyoshi; Sugito, Hiroki; Nagayama, Motohiko; Kuboki, Takuo; Pacifici, Maurizio; Koyama, Eiki.
In: Archives of Oral Biology, Vol. 58, No. 11, 2013, p. 1659-1666.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of CCN2 gene expression and possible roles in developing tooth germs
AU - Kanyama, Manabu
AU - Shimo, Tsuyoshi
AU - Sugito, Hiroki
AU - Nagayama, Motohiko
AU - Kuboki, Takuo
AU - Pacifici, Maurizio
AU - Koyama, Eiki
PY - 2013
Y1 - 2013
N2 - CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100 ng/μl was able to induce strong CCN2 expression while a minimum concentration of 25 ng/μl was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme.
AB - CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100 ng/μl was able to induce strong CCN2 expression while a minimum concentration of 25 ng/μl was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme.
KW - BMP
KW - CCN
KW - CCN2
KW - FGF
KW - Tooth development
UR - http://www.scopus.com/inward/record.url?scp=84884770559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884770559&partnerID=8YFLogxK
U2 - 10.1016/j.archoralbio.2013.08.010
DO - 10.1016/j.archoralbio.2013.08.010
M3 - Article
VL - 58
SP - 1659
EP - 1666
JO - Archives of Oral Biology
JF - Archives of Oral Biology
SN - 0003-9969
IS - 11
ER -