title: FoxOs, Wnts and oxidative stress-induced bone loss: new players in the periodontitis arena?
abstract: OBJECTIVE
  Chronic periodontitis is a widespread disease affecting tooth-supporting structures that can lead to extensive loss of periodontal ligament and bone, ultimately resulting in tooth loss. Extensive evidence has demonstrated a strong association between age, metabolic disorders such as type II diabetes, oxidative stress and alveolar bone loss. The molecular players controlling bone maintenance and underlying age-related bone loss and its links to the general metabolism are currently the object of intense research.
  
  
  METHODS
  Recent findings are summarized to elucidate the molecular mechanisms linking oxidative stress, bone loss and metabolic factors.
  
  
  RESULTS
  It is well known that reactive oxygen species are an inevitable consequence of cellular respiration and that organisms have developed an efficient array of defenses against them. The core of this complex defense line is a family of transcription factors, known as FoxOs, which can bind to β-catenin and initiate a transcriptional programme regulating cell apoptosis, DNA repair and degradation of reactive oxygen species. An increase in reactive oxygen species due, for example, to age or insulin resistance, generates a situation in which bone formation is impaired by activation of FoxO, and a decrease in Wnt signaling and bone resorption are promoted.
  
  
  CONCLUSIONS
  The balance between FoxO and the Wnt pathway is finely tuned by systemic and local factors, creating a far-reaching mechanism that dictates the fate of mesenchymal progenitors and regulates the homeostasis of bone, providing a rationale for the impairment of systemic and alveolar bone maintenance clinically observed with age and metabolic diseases.
authors.affiliation: Department of Internal Medicine Unit of Periodontology, University of Parma, Parma, Italy. carlo.galli@unipr.it
authors.forename: C
authors.initials: C
authors.lastname: Galli
authors.forename: G
authors.initials: G
authors.lastname: Passeri
authors.forename: G M
authors.initials: GM
authors.lastname: Macaluso
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology*; D055113:Chronic Periodontitis / Q000209:etiology*; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
chemical_list: D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; D051153:Wnt Proteins; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt