Tooth Movement Modulation and Root Protection via Piezo1‐Mediated Production of Superoxide Dismutase 3

AIMS: This study investigated the role of superoxide dismutase 3 (SOD3) in alveolar bone remodeling and cementum repair under orthodontic loading. METHODS: Mice were subjected to models of tooth movement with or without adenovirus-SOD3 treatment, and were examined for osteolytic activity, distance of tooth movement, and volume of root resorption. The periodontal ligament cells (PDLCs) were cultured under mechanical loading or unloaded controls, in the presence or absence of piezo-type mechanosensitive ion channel component1 (Piezo1) inhibitor GsMTx4 or Yes-associated protein (YAP) inhibitor Verteporfin, and were examined for SOD3 expressions. The MC3T3-E1, BMSCs, OCCM-30, BMMs, and RAW264.7 cell cultures with or without recombinant mouse SOD3 (rmSOD3) administration were examined for osteogenic or osteoclastogenic markers. RESULTS: Orthodontic loading induced SOD3 expressions in the periodontal ligament (PDL). The mechanical force-induced production of SOD3 in the PDLCs was potentially mediated by Piezo1 and YAP signaling. Exogenous rmSOD3 promoted osteoblastogenesis, boosted cementoblast differentiation and mineralization, and inhibited osteoclastogenesis from osteoclast precursors. Adenovirus-mediated SOD3 overexpression in the PDL suppressed osteoclast differentiation, reduced root resorption, and retarded orthodontic tooth movement. CONCLUSION: Piezo1-mediated production of SOD3 from the PDLCs protected the root from resorption and retarded tooth movement by suppressing osteoclastogenesis and promoting osteoblast and cementoblast differentiation.