Insulin-like growth factor 1 and transforming growth factor-ß stimulate cystine/glutamate exchange activity in dental pulp cells.

INTRODUCTION: The growth factors insulin-like growth factor (IGF-1) and transforming growth factor-ß (TGF-ß) are protective to dental pulp cells in culture against the toxicity of the composite materials Durafill VS and Flow Line (Henry Schein Inc, New York, NY). Because the toxicity of these materials is mediated by oxidative stress, it seemed possible that the protective effects of IGF-1 and TGF-ß were through the enhancement of an endogenous antioxidant mechanism. METHODS: We used cultured dental pulp cells to determine the mechanism of the protective effects of IGF-1 and TGF-ß, focusing on the glutathione system and the role of cystine/glutamate exchange (system xc-). RESULTS: We found that the toxicity of Durafill VS and Flow Line was attenuated by the addition of glutathione monoethylester, suggesting a specific role for the cellular antioxidant glutathione. Supporting this hypothesis, we found that IGF-1 and TGF-ß were protective against the toxicity of the glutathione synthesis inhibitor buthionine sulfoximine. Because levels of cellular cystine are the limiting factor in the production of glutathione, we tested the effects of IGF-1 and TGF-ß on cystine uptake. Both growth factors stimulated system xc-mediated cystine uptake. Furthermore, they attenuated the glutathione depletion induced by Durafill VS and Flow Line. CONCLUSIONS: The results suggest that IGF-1 and TGF-ß are protective through the stimulation of system xc-mediated cystine uptake, leading to maintenance of cellular glutathione. This novel action of growth factors on dental pulp cells has implications not only for preventing toxicity of dental materials but also for the general function of these cells.

Toxicity of Flow Line, Durafill VS, and Dycal to dental pulp cells: effects of growth factors.

INTRODUCTION: The objective was to determine the effects of growth factor treatment on dental pulp cell sensitivity to toxicity of 2 composite restoration materials, Flow Line and Durafill VS, and a calcium hydroxide pulp capping material, Dycal. METHODS: Toxicity of the dental materials to cultures of primary dental pulp cells was determined by the MTT metabolism assay. The ability of 6 different growth factors to influence the toxicity was tested. RESULTS: A 24-hour exposure to either Flow Line or Durafill VS caused approximately 40% cell death, whereas Dycal exposure caused approximately 80% cell death. The toxicity of Flow Line and Durafill VS was mediated by oxidative stress. Four of the growth factors tested (bone morphogenetic protein [BMP]-2, BMP-7, epidermal growth factor [EGF], and transforming growth factor [TGF]-beta) decreased the basal MTT values while making the cells resistant to Flow Line and Durafill VS toxicity except BMP-2, which made the cells more sensitive to Flow Line. Treatment with fibroblast growth factor-2 caused no change in basal MTT metabolism, prevented the toxicity of Durafill VS, but increased the toxicity of Flow Line. Treatment with insulin-like growth factor-I (IGF-I) increased basal MTT metabolism and made the cells resistant to Flow Line and Durafill VS toxicity. None of the growth factors made the cells resistant to Dycal toxicity. CONCLUSIONS: The results indicated that growth factors can be used to alter the sensitivity of dental pulp cells to commonly used restoration materials. The growth factors BMP-7, EGF, TGF-beta, and IGF-I provided the best profile of effects, making the cells resistant to both Flow Line and Durafill VS toxicity.