Details

Autor(en) / Beteiligte

• Gkouveris, Ioannis
• Hadaya, Danny
• Soundia, Akrivoula
• Bezouglaia, Olga
• Chau, Yee
• Dry, Sarah M.
• Pirih, Flavia Q.
• Aghaloo, Tara L.
• Tetradis, Sotirios

Titel

Vasculature submucosal changes at early stages of osteonecrosis of the jaw (ONJ)

Ist Teil von

• Bone (New York, N.Y.), 2019-06, Vol.123, p.234-245

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Osteonecrosis of the jaw (ONJ), a rare, but potentially severe side effect of anti-resorptive medications, presents as exposed bone in the maxillofacial region lasting for at least 8 weeks. While clinical experience and animal models concur in finding that systemic antiresorptive treatment in conjunction with local risk factors, such as tooth extraction or dental disease may lead to ONJ development, the subclinical molecular changes that precede bone exposure remain poorly understood. The identification of these changes is not only important in understanding disease pathophysiology, but could provide potential for treatment development. Here, we evaluated the early stages of ONJ utilizing a model of experimental periodontitis (EP) in mice treated with two different types of antiresorptives, targeting potential changes in vasculature, hypoxia, oxidative stress, and apoptosis. Antiresorptive treatment in animals with EP increased levels of empty osteocytic lacunae and increased ONJ prevalence compared to Veh animals. The arteriole and venule network seen around EP areas was diminished in animals treated with antiresorptives. Higher levels of vascular endothelial growth factor A (VEGF-A) and vascular cell adhesion protein-1 (VCAM-1) were observed 1-week following EP in treated animals. Finally, levels of hypoxia, oxidative stress, and apoptosis remained high in antiresorptive treated animals with EP through the duration of the experiment. Together, our data point to subclinical vasculature organizational disturbances that subsequently affect levels of hypoxia, oxidative stress, and apoptosis in the area of developing ONJ. •Mice treated with antiresorptives undergo subclinical, molecular changes prior to the development of clinical ONJ lesions.•Alterations in the vasculature networks were present around areas of developing ONJ one-week following disease induction.•HIF-1a, VEGF and VCAM showed a temporal regulation of expression during ONJ development.•High levels of cell apoptosis and oxidative stress were observed in the submucosal tissues around areas of osteonecrosis.•Structural vasculature changes with altered responses to hypoxia, oxidative stress and apoptosis precede ONJ development.