Abstract
Adiponectin is an adipokine that sensitizes the body to insulin. Low levels of adiponectin have been reported in obesity, diabetes and periodontitis. In this study we established experimental periodontitis in male adiponectin knockout and diet-induced obesity mice, a model of obesity and type 2 diabetes, and aimed at evaluating the therapeutic potential of adiponectin. We found that systemic adiponectin infusion reduced alveolar bone loss, osteoclast activity and infiltration of inflammatory cells in both periodontitis mouse models. Furthermore, adiponectin treatment decreased the levels of pro-inflammatory cytokines in white adipose tissue of diet-induced obesity mice with experimental periodontitis. Our in vitro studies also revealed that forkhead box O1, a key transcriptional regulator of energy metabolism, played an important role in the direct signaling of adiponectin in osteoclasts. Thus, adiponectin increased forkhead box O1 mRNA expression and its nuclear protein level in osteoclast-precursor cells undergoing differentiation. Inhibition of c-Jun N-terminal kinase signaling decreased nuclear protein levels of forkhead box O1. Furthermore, over-expression of forkhead box O1 inhibited osteoclastogenesis and led to decreased nuclear levels of nuclear factor of activated T cells c1. Taken together, this study suggests that systemic adiponectin application may constitute a potential intervention therapy to ameliorate type 2 diabetes-associated periodontitis. It also proposes that adiponectin inhibition of osteoclastogenesis involves forkhead box O1.
Highlights
Periodontitis is an inflammatory disease that involves progressive loss of alveolar bone around the teeth and can result in tooth loss
Our results showed that alveolar bone loss was significantly increased upon induction of experimental periodontitis in male WT and APN2/2 mice (Figure 1A, P,0.05), indicating that periodontitis was successfully established
There was no significant difference in alveolar bone loss between WT and APN2/2 mice induced with periodontitis, Tartrate-Resistant Acid Phosphatase (TRAP)-stained palatal bone samples from APN2/2 mice with periodontitis exhibited a higher number of osteoclasts than in those derived from WT mice induced with experimental periodontitis (Figure 1B, P,0.05)
Summary
Periodontitis is an inflammatory disease that involves progressive loss of alveolar bone around the teeth and can result in tooth loss It is twice as prevalent in diabetics as in non-diabetics, and has been rated as the sixth complication of diabetes [1]. Excess white adipose tissue (WAT) in obese is characterized by increased macrophage infiltration and production of proinflammatory cytokines including tumor necrosis factor-a (TNF-a) and interleukine-6 (IL-6) that mediate local and systemic effects on inducing insulin resistance [2]. This systemic inflammation and insulin resistance in T2D contributes to the pathogenesis of periodontitis [1,3]. Developing an effective therapeutic treatment for T2D-associated periodontitis that can both inhibit bone resorption and decrease inflammation is critically important
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