Peroxisome proliferator-activated receptor gamma preserves intracellular homeostasis of insulin-resistant periodontal ligament stem cells.

Abstract

BackgroundDiabetes and periodontitis develop and influence each other. The peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone (RSG) controls blood glucose and hence the systemic diseases associated with diabetes by increasing the sensitivity of tissues to insulin. However, whether and how RSG can treat diabetic periodontitis is poorly understood.MethodsInsulin-resistant periodontal ligament stem cells (IR-PDLSCs) were induced by glucosamine (18 mM, 24 h) in the presence or absence of RSG or GW9662 (a PPARγ antagonist). The glucose uptake rate was tested to evaluate insulin sensitivity. A scratch test was carried out to measure cell proliferation and motility. We used 2,7-dichlorodihydrofluorescein diacetate (DFCH-DA) and JC-1 kits to detect oxidative stress (OS), and cytoskeleton staining and Calcein-AM/PI kits were used to determine cell viability. Interferon-gamma (IFN-γ) and interleukin-10 (IL-10) ELISA kits were used to evaluate inflammation levels. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analysis were used to assess the expression of osteogenic/odontogenic differentiation-related genes or proteins.ResultsOur results showed that RSG exhibited a protective effect on IR-PDLSCs, with increased insulin sensitivity and migration efficiency, an alleviation of glucosamine-induced OS, and a downregulated pro-inflammatory cytokine secretion through activation of PPARγ receptors. Moreover, RSG alleviated the suppressed odontogenic differentiation ability of IR-PDLSCs.ConclusionsRSG preserves the biological functions of IR-PDLSCs in maintaining intracellular homeostasis by increasing insulin sensitivity, reducing OS, and suppressing inflammation.