title: Focal adhesion kinase mediates β-catenin signaling in periodontal ligament cells.
abstract: Periodontal ligament (PDL) cells convert the orthodontic forces into biological responses by secreting signaling molecules to induce modeling of alveolar bone and tooth movement. Beta-catenin pathway is activated in response to mechanical loading in PDL cells. The upstream signaling pathways activated by mechanical loading resulting in the activation of β-catenin pathway through Wnt-independent mechanism remains to be characterized. We hypothesized that mechanical loading induces activation of β-catenin signaling by mechanisms that dependent on focal adhesion kinase (FAK) and nitric oxide (NO). We found that mechanical or pharmacological activation of β-catenin signaling in PDL cells upregulated the expression of β-catenin target genes. Pre-treatment of PDL cells with FAK inhibitor-14 prior to mechanical loading abolished the mechanical loading-induced phosphorylation of Akt and dephosphorylation of β-catenin. PDL cells pre-treated with NO donor or NO inhibitor and subjected to mechanical loading. Western blot analysis showed that the mechanical loading or pre-treatment with NO donor increased the levels of dephosphorylated β-catenin, pAkt, and pGSK-3β. Pre-treatment with NO inhibitor blocked the mechanical loading-induced phosphorylation of Akt and dephosphorylation of β-catenin. These data indicate that mechanical loading-induced β-catenin stabilization in PDL cells involves phosphorylation of Akt by two parallel pathways requiring FAK and NO.
authors.affiliation: Department of Growth and Development, University of Nebraska Medical Center College of Dentistry, Lincoln, NE, USA. Electronic address: spremaraj@unmc.edu.
authors.forename: Sundaralingam
authors.initials: S
authors.lastname: Premaraj
authors.forename: Isabela
authors.initials: I
authors.lastname: Souza
authors.forename: Thyagaseely
authors.initials: T
authors.lastname: Premaraj
mesh_terms: D002460:Cell Line; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010513:Periodontal Ligament / Q000201:enzymology / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; D051176:beta Catenin; D019938:Cyclin D1; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt signaling; COX-2; Mechanotransduction; Nitric oxide; Periodontal ligament cell; Prostaglandin E(2); Tooth movement; β-catenin signaling