• Home
  • Search Results
  • Mutation of Spry2 induces proliferation and differentiation of osteoblasts but inhibits proliferation of gingival epithelial cells.

Mutation of Spry2 induces proliferation and differentiation of osteoblasts but inhibits proliferation of gingival epithelial cells.

Journal of cellular biochemistry (2014-11-18)
Terukazu Sanui, Urara Tanaka, Takao Fukuda, Kyosuke Toyoda, Takaharu Taketomi, Ryo Atomura, Kensuke Yamamichi, Fusanori Nishimura
ABSTRACT

Sprouty was identified as an inhibitor of the fibroblast growth factor (FGF) receptor, and Sprouty2 (Spry2) functions as a negative regulator of receptor tyrosine kinase signaling. In this study, we investigated how inhibition of Spry2 affects osteoblasts and gingival epithelial cells in periodontal tissue regeneration in vitro. Transduction of a dominant-negative mutant of Spry2 (Y55A-Spry2) enhanced basic fibroblast growth factor (bFGF)- and epidermal growth factor (EGF)-induced ERK activation in MC3T3-E1 osteoblastic cells. In contrast, it decreased their activation in GE1 cells. Consistent with these observations, Y55A-Spry2 increased osteoblast proliferation with bFGF and EGF stimulation, whereas the proliferation of Y55A-Spry2-introduced GE1 cells was decreased via the ubiquitination and degradation of EGF receptors (EGFRs). In addition, Y55A-Spry2 caused upregulation of Runx2 expression and downregulation of Twist, a negative regulator of Runx2, with treatment of bFGF and EGF, resulting in enhanced osteoblastogenesis accompanied by alkaline phosphatase activation and osteocalcin expression in MC3T3-E1 cells. These data suggest that suppression of Spry2 expression induces proliferation and differentiation of osteoblastic cells after the addition of a bFGF and EGF cocktail but inhibits proliferation in gingival epithelial cells. These in vitro experiments may provide a molecular basis for novel therapeutic approaches in periodontal tissue regeneration. Taken together, our study proposes that combined application of an inhibitor for tyrosine 55 of Spry2, bFGF, and EGF may effectively allow alveolar bone growth and block the ingrowth of gingival epithelial cells toward bony defects, biologically mimicking a barrier effect in guided tissue regeneration, with in vivo investigation in the future.

MATERIALS
Product Number
Brand
Product Description

Glutathione, European Pharmacopoeia (EP) Reference Standard
Supelco
L-Ascorbic acid, certified reference material, TraceCERT®
Supelco
Glutathione, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Ascorbic acid, powder, suitable for cell culture, γ-irradiated
Sigma-Aldrich
L-Ascorbic acid, suitable for plant cell culture
Sigma-Aldrich
L-Ascorbic acid, BioXtra, ≥99.0%, crystalline
Sigma-Aldrich
L-Ascorbic acid, reagent grade, crystalline
Sigma-Aldrich
L-Ascorbic acid, suitable for cell culture, suitable for plant cell culture, ≥98%
Sigma-Aldrich
L-Ascorbic acid, reagent grade
Sigma-Aldrich
L-Ascorbic acid, meets USP testing specifications
Sigma-Aldrich
L-Ascorbic acid, puriss. p.a., ACS reagent, reag. ISO, Ph. Eur., 99.7-100.5% (oxidimetric)
Supelco
L-Ascorbic acid, analytical standard
Sigma-Aldrich
Edelfosine, ≥95% (HPLC)
Sigma-Aldrich
L-Ascorbic acid, 99%
Sigma-Aldrich
L-Ascorbic acid, ACS reagent, ≥99%
Sigma-Aldrich
L-Ascorbic acid, puriss. p.a., ≥99.0% (RT)
Sigma-Aldrich
L-Ascorbic acid, tested according to Ph. Eur.
Sigma-Aldrich
L-Ascorbic acid, BioUltra, ≥99.5% (RT)
Sigma-Aldrich
L-Ascorbic acid, FCC, FG
Ascorbic acid, European Pharmacopoeia (EP) Reference Standard
USP
Ascorbic acid, United States Pharmacopeia (USP) Reference Standard
Supelco
Ascorbic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Glutathione reduced, BioXtra, ≥98.0%
Sigma-Aldrich
L-Glutathione reduced, ≥98.0%
Sigma-Aldrich
L-Glutathione reduced, BioReagent, suitable for cell culture, ≥98.0%, powder