Impact of Myeloid HIF-1α on Orthodontic Tooth Movement in Mice

Objectives: The transcription factor hypoxia inducible factor 1α (HIF1α) is stabilized by a lack of oxygen and controls the adaptation of tissue to hypoxic conditions through targeted expression of genes. During orthodontic tooth movement, forces are exerted on the tooth to be moved and tension and pressure zones are created in the periodontal ligament. In addition to periodontal ligament fibroblasts, which comprise the main cell population in the periodontal ligament, immune cells such as macrophages are also exposed to these mechanical loads. While HIF1α in periodontal ligament fibroblasts can be stabilized not only by a reduced oxygen levels, but also by mechanical compression, pressure application alone is not sufficient to stabilize HIF1α in macrophages as previously shown. The present study was carried out to investigate the role of myeloid HIF1α during orthodontic tooth movement.
Methods: In 20 wild-type mice (WT) and 20 HIF1α-floxed LysMCRE mice without HIF1α expression in myeloid cells (Hif1αΔmyel) an elastic rubber band was inserted at the left upper jaw side between the 1st and 2nd molars and left in situ for 7 days to induce experimental orthodontic tooth movement. The right jaw side served as control (split-mouth design). µCT was performed to determine periodontal bone loss, tooth movement and bone density. RNA was isolated from the periodontal ligament at the control side and the orthodontically treated side and the expression of genes involved in bone remodeling was examined.
Results: The extent of tooth movement was increased in Hif1αΔmyel mice. This could be due to a lower bone density of the Hif1αΔmyel mice. The deletion of myeloid Hif1α was associated with an increased expression of Ctsk and Acp5, while expression of both Rankl and its decoy receptor Opg were increased.
Conclusions: HIF1α from myeloid cells appears to play a regulatory role in orthodontic tooth movement.