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2017 ; 7
(ä): 45181
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Nephronectin plays critical roles in Sox2 expression and proliferation in dental
epithelial stem cells via EGF-like repeat domains
#MMPMID28345658
Arai C
; Yoshizaki K
; Miyazaki K
; Saito K
; Yamada A
; Han X
; Funada K
; Fukumoto E
; Haruyama N
; Iwamoto T
; Takahashi I
; Fukumoto S
Sci Rep
2017[Mar]; 7
(ä): 45181
PMID28345658
show ga
Tooth development is initiated by epithelial-mesenchymal interactions via
basement membrane (BM) and growth factors. In the present study, we found that
nephronectin (Npnt), a component of the BM, is highly expressed in the developing
tooth. Npnt localizes in the BM on the buccal side of the tooth germ and shows an
expression pattern opposite that of the dental epithelial stem cell marker Sox2.
To identify the roles of Npnt during tooth development, we performed knockdown
and overexpression experiments using ex vivo organ and dental epithelial cell
cultures. Our findings showed that loss of Npnt induced ectopic Sox2-positive
cells and reduced tooth germ size. Over expression of Npnt showed increased
proliferation, whereas the number of Sox2-positive cells was decreased in dental
epithelial cells. Npnt contains 5 EGF-like repeat domains, as well as an RGD
sequence and MAM domain. We found that the EGF-like repeats are critical for Sox2
expression and cell proliferation. Furthermore, Npnt activated the EGF receptor
(EGFR) via the EGF-like repeat domains and induced the PI3K-Akt signaling
pathway. Our results indicate that Npnt plays a critical scaffold role in dental
epithelial stem cell differentiation and proliferation, and regulates Sox2
expression during tooth development.