Abstract
Our study seeks to explore anabolic effects of a periodontal regenerative agent enamel matrix derivative (EMD). Its modulation by nicotine and the anti-oxidant glutathione (GSH) are investigated in human periosteal fibroblasts (HPF) and MG63 osteoblasts. Androgen biomarkers of oxidative stress and healing, resulting from radiolabeled androgen substrates are assayed. This in vitro model simulates a redox environment relevant to the periodontal lesion. It aims to confirm the hypothesis that EMD is an effective regenerative agent in a typically redox environment of the periodontal lesion. Monolayer cultures of MG63 osteoblasts and HPF established in culture medium are incubated with androgen substrates, and optimal concentrations of EMD, nicotine and GSH, alone and in combination. EMD significantly enhances yields of 5α-dihydrotestosterone (DHT) an effective bioactive metabolite, alone and in combination with GSH, to overcome oxidative effects of nicotine across cultures. The ‘in vitro’ findings of this study could be extrapolated to “in vivo” applications of EMD as an adjunctive regenerative therapeutic agent in an environment of chronic inflammation and oxidative stress. Increased yields of DHT implicated in matrix synthesis and direct antioxidant capacity, confirm the potential applications for enamel matrix derivative in periodontal regenerative procedures.
Highlights
The aim of this in vitro investigation is to study anabolic responses to enamel matrix derivative (EMD) in human periosteal fibroblasts and osteoblasts in a redox environment, using radiolabeled steroid substrates
Down-regulation of genes associated with the early inflammatory phase of periodontal wound healing is attributed to EMD, with simultaneous up-regulation of genes encoding for molecules that promote growth and repair [4]
When monolayer cultures of MG63 osteoblasts were incubated with 14C-T as substrate with serial concentrations of EMD ranging from 15–75 μg/mL, the main metabolites formed in response to EMD
Summary
The aim of this in vitro investigation is to study anabolic responses to enamel matrix derivative (EMD) in human periosteal fibroblasts and osteoblasts in a redox environment, using radiolabeled steroid substrates. The actions of EMD in an inflammatory environment are relevant to its effects in regenerating periodontal bone defects. The rationale for this investigation is supported by the actions of the agents studied with potential for extrapolation to the in vivo environment. Relevant background on agents used in this study and their potential applications are provided here. The scientific basis for the regenerative actions of EMD and clinical application in periodontal recession defects are documented [1,2]. Down-regulation of genes associated with the early inflammatory phase of periodontal wound healing is attributed to EMD, with simultaneous up-regulation of genes encoding for molecules that promote growth and repair [4]
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