Runx1/miR-26a/Jagged1 signaling axis controls osteoclastogenesis and alleviates orthodontically induced inflammatory root resorption.

BACKGROUND: MicroRNAs (miRNAs) are involved in the regulation of osteoclast biology and several pathogenic progression. This study aimed to identify the role of miR-26a in osteoclastogenesis and orthodontically induced inflammatory root resorption(OIIRR).

METHODS: Rat orthodontic tooth movement (OTM) model was established by ligating a closed coil spring between maxillary first molar and incisor, and 50 g orthodontic force was applied to move upper first molar to middle for 7 days. Human periodontal ligament (hPDL) cells were isolated from periodontium of healthy donors, and then subjected to compression force (CF) for 24 h to mimic an in vitro OTM model. The levels of associated factors in vivo and in vitro were measured subsequently.

RESULT: The distance of tooth movement was increased and root resorption pits were occurred in rat OTM model. The expression of miR-26a was decreased in vivo and vitro experiments. CF treatment enhanced the secretion of inflammatory factors receptor activator of nuclear factor-kappa B ligand (RANKL) and IL-6, osteoclast marker levels, and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, while miR-26a overexpression reversed these results. Furthermore, miR-26a overexpression inhibited the osteoclastogenesis and rescued the root resorption in OTM rats through inhibition of Jagged1. Additionally, Runx1 could bind to miR-26a promoter and promote its expression, thereby suppressing the osteoclastogenesis.

CONCLUSION: We concluded that Runx1/miR-26a/Jagged1 signaling axis restrained osteoclastogenesis and alleviated OIIRR.