Occlusal hypofunction mediates alveolar bone apposition via relative augmentation of TGF-β signaling by decreased Asporin production in rats

The periodontal ligament (PDL) maintains alveolar bone homeostasis against mastication force. Occlusal hypofunction, which lost mastication force, narrows the PDL by alveolar bone apposition, though the mechanisms remain unclear. Asporin is a secreted extracellular matrix protein and preferentially expressed in the PDL. Asporin binds directly with transforming growth factor-beta (TGF-β) and inhibits TGF-β/Smad signaling, resulting in the inhibition of bone formation. In the present study, we hypothesized that Asporin is downregulated by occlusal hypofunction, which results in the increased alveolar bone apposition via relative upregulation of TGF-β signaling. To clarify the hypothesis, we employed in vivo experiments using rats. Crowns of lower right first molar in Wistar rats were removed to induce occlusal hypofunction in upper right first molar. Alveolar bone apposition was examined by histomorphometric analysis of Calcein/Xylenol-orange vital staining. Asporin, TGF-β, and it`s signaling molecule, Smad3 expression were examined in mRNA and protein levels. Osteoblastic differentiation of the cell in the PDL under the occlusal hypofunction were observed using Bone sialoprotein (BSP), Osteocalcin and Osteopontin expression as osteoblastic differentiation marker. We discovered that occlusal hypofunction increased the alveolar bone apposition and downregulated Asporin expression in PDL fibroblasts. Furthermore, occlusal hypofunction relative augmented TGF-β signaling in PDL judged by phosphorylated (p)-Smad2/3 immunohistochemical staining, and upregulated osteoblastic differentiation in PDL. In the present study, we firstly reported that occlusal hypofunction mediates alveolar bone apposition via relative augmentation of TGF-β signaling by decrease of Asporin production. Correspondence to: Yoshiki Nakamura, DDS, Ph D, Department of orthodontics, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa pref., 230-8501, Japan, Tel: +81-45-580-8507, Fax: +8145-573-9599, E-mail: [email protected]