The role of insulin-like growth factors (IGFs) in the regulation of apoptosis has been suggested, yet their impact on specific cells such as periodontal ligament fibroblasts (PDLF) and gingival fibroblasts (GF) remains unknown. The purpose of this study was to test the role of IGF-1 signaling in cell survival in PDLF compared with GF. In periodontal tissue sections, a significantly reduced apoptotic rate was first demonstrated in PDLF compared with GF. In vitro, IGF-1 substantially enhanced cell survival in PDLF compared with GF by the up-regulation of anti-apoptotic molecules and the down-regulation of pro-apoptotic molecules. Furthermore, the differential expression of insulin-like growth factor binding protein 5 (IGFBP-5) was observed in vitro, and its differential distribution was confirmed in vivo. Analysis of the present data suggests an enhanced cell survival in PDLF compared with GF by the up-regulation of IGF-1 signaling pathway.
Get full access to this article
View all access options for this article.
References
1.
Andress DL -1998-. Insulin-like growth factor-binding protein-5 -IGFBP-5- stimulates phosphorylation of the IGFBP-5 receptor. Am J Physiol274:E744–E750.
Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al. -1997-. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell91:231–241.
4.
Drexler HC -1997-. Activation of the cell death program by inhibition of proteasome function. Proc Natl Acad Sci USA94:855–860.
5.
Gagnon A, Dods P, Roustan-Delatour N, Chen CS, Sorisky A -2001-. Phosphatidylinositol-3,4,5-trisphosphate is required for insulin-like growth factor 1-mediated survival of 3T3-L1 preadipocytes. Endocrinology42:205–212.
6.
Haase HR, Clarkson RW, Waters MJ, Bartold PM -1998-. Growth factor modulation of mitogenic responses and proteoglycan synthesis by human periodontal fibroblasts. J Cell Physiol174:353–361.
7.
Han X, Amar S -2002-. Identification of genes differentially expressed in cultured human periodontal ligament fibroblasts vs. human gingival fibroblasts by DNA microarray analysis. J Dent Res81:399–405.
8.
Hansen JB, Petersen RK, Jørgensen C, Kristiansen K -2002-. Deregulated MAPK activity prevents adipocyte differentiation of fibroblasts lacking the retinoblastoma protein. J Biol Chem277:26335–26339.
9.
Hatai T, Matsuzawa A, Inoshita S, Mochida Y, Kuroda T, Sakamaki K, et al. -2000-. Execution of apoptosis signal-regulating kinase 1 -ASK1--induced apoptosis by the mitochondria-dependent caspase activation. J Biol Chem275:26576–26581.
10.
Huang DC, Strasser A -2000-. BH3-only proteins—essential initiators of apoptotic cell death. Cell103:839–842.
11.
Ivanovski S, Haase HR, Bartold PM -2001-. Isolation and characterization of fibroblasts derived from regenerating human periodontal defects. Arch Oral Biol46:679–688.
12.
Korsmeyer SJ -1999-. BCL-2 gene family and the regulation of programmed cell death. Cancer Res59:1693s–1700s.
13.
Lackler KP, Cochran DL, Hoang AM, Takacs V, Oates TW -2000-. Development of an in vitro wound healing model for periodontal cells. J Periodontol71:226–237.
14.
Lekic PC, Pender N, McCulloch CA -1997-. Is fibroblast heterogeneity relevant to the health, diseases, and treatments of periodontal tissues? Crit Rev Oral Biol Med8:253–268.
15.
Lynch SE, de Castilla GR, Williams RC, Kiritsy CP, Howell TH, Reddy MS, et al. -1991-. The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. J Periodontol62:458–467.
16.
Meadows KA, Holly JM, Stewart CE -2000-. Tumor necrosis factor-alpha-induced apoptosis is associated with suppression of insulin-like growth factor binding protein-5 secretion in differentiating murine skeletal myoblasts. J Cell Physiol183:330–337.
17.
Miyake H, Nelson C, Rennie PS, Gleave ME -2000-. Overexpression of insulin-like growth factor binding protein-5 helps accelerate progression to androgen-independence in the human prostate LNCaP tumor model through activation of phosphatidylinositol 3’-kinase pathway. Endocrinology41:2257–2265.
18.
Miyakoshi N, Richman C, Kasukawa Y, Linkhart TA, Baylink DJ, Mohan S -2001-. Evidence that IGF-binding protein-5 functions as a growth factor. J Clin Invest107:73–81.
19.
Mumford JH, Carnes DL, Cochran DL, Oates TW -2001-. The effects of platelet-derived growth factor-BB on periodontal cells in an in vitro wound model. J Periodontol72:331–340.
20.
Nishimura F, Terranova VP -1996-. Comparative study of the chemotactic responses of periodontal ligament cells and gingival fibroblasts to polypeptide growth factors. J Dent Res75:986–992.
21.
Parrizas M, Saltiel AR, LeRoith D -1997-. Insulin-like growth factor 1 inhibits apoptosis using the phosphatidylinositol 3’-kinase and mitogen-activated protein kinase pathways. J Biol Chem272:154–161.
22.
Perks CM, McCaig C, Holly JM -2000-. Differential insulin-like growth factor -IGF--independent interactions of IGF binding protein-3 and IGF binding protein-5 on apoptosis in human breast cancer cells. Involvement of the mitochondria. J Cell Biochem80:248–258.
23.
Roschier M, Kuusisto E, Suuronen T, Korhonen P, Kyrylenko S, Salminen A -2001-. Insulin-like growth factor binding protein 5 and type-1 insulin-like growth factor receptor are differentially regulated during apoptosis in cerebellar granule cells. J Neurochem76:11–20.
24.
Santiago B, Galindo M, Rivero M, Pablos JL -2001-. Decreased susceptibility to Fas-induced apoptosis of systemic sclerosis dermal fibroblasts. Arthritis Rheum44:1667–1676.
25.
Schedlich LJ, Le Page SL, Firth SM, Briggs LJ, Jans DA, Baxter RC -2000-. Nuclear import of insulin-like growth factor-binding protein-3 and -5 is mediated by the importin beta subunit. J Biol Chem275:23462–23470.
26.
Wang X -2001-. The expanding role of mitochondria in apoptosis. Genes Dev15:2922–2933.
