Mechanical Force-Stimulated Dental Pulp Cells Enhance Osteoclastogenesis via S100A7

Objectives: Mechanical injuries, such as dental trauma, uncontrolled orthodontic force, and chronic parafunctional force stimulate inflammatory response of hDPCs (human dental pulp cells), which induce osteoclastogenesis/odontoclastogenesis and consequently lead to root resorption. One feasible molecular mechanism that provokes inflammatory process in response to mechanical injuries is through DAMPs (danger associated molecular patterns). S100A7 is a DAMP that may play a role on osteoclastogenesis/odontoclastogenesis and root resorption. Our objectives are to determine the mRNA and protein level of S100A7 in mechanical force-stimulated hDPCs and to investigate the effect of S100A7 on osteoclast formation and function.
Methods: hDPCs were isolated from freshly extracted third molar. The cells were subjected to 0, 1 and 2 g/cm² of continuous force for 2, 6 and 16 h. Then, S100A7 mRNA and protein level were determined by quantitative real-time PCR and ELISA, respectively. To investigate osteoclast formation and function in vitro, human CD14⁺ PBMCs were isolated and differentiated into osteoclasts for 14 days in the presence of various amount of S100A7, and TRAP staining and resorption pit assay were performed.
Results: S100A7 mRNA expression in hDPCs was significantly upregulated at 2 h (P<0.05), and the protein production was markedly enhanced at 6 and 16 h (P<0.05) after mechanical force application. The increased size and number of osteoclasts were observed when treated the cells with S100A7 (P<0.05). Consistently, S100A7-treated osteoclasts also showed the increased resorption pit number and area in a dose-dependent manner (P<0.05).
Conclusions: The results suggest that mechanical force-stimulated hDPCs possibly enhance osteoclast formation and function via S100A7. Our study firstly clarify the cellular and molecular mechanism of root resorption from mechanical injuries. These findings beneficially contribute to clinical therapeutic application by specific targeting on DAMP-associated osteoclastogenesis/odontoclastogenesis.