Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement

Abstract

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.

Impact of Myeloid p38α/MAPK on Orthodontic Tooth Movement

“…No influence of orthodontic tooth movement or deletion of p38α/MAPK on Opg gene expression was observed. This was in line with previous studies reporting that orthodontic treatment did not affect Opg expression in periodontal tissue [ 19 , 24 , 25 ]. Periodontal ligament fibroblasts react to mechanical strain in vitro with a reduction of Opg gene expression [ 27 ].…”

“…Macrophages were shown to react to mechanical stress with increased secretion of inflammatory factors like tumor necrosis factor, interleukin-6 (IL6), and prostaglandin E2 [ 6 ]. Here, no effects of orthodontic tooth movement on Tnf gene expression were detected, while Il6 and prostaglandin endoperoxide synthase 2 ( Ptgs2 ) were upregulated on the orthodontically treated maxillary jaw side, which was in line with several previous studies [ 19 , 24 , 25 ]. However, involvement of p38α/MAPK in this mechanically-induced upregulation has not been tested so far.…”

Anti-osteoporosis effects and regulatory mechanism of Lindera aggregata based on network pharmacology and experimental validation

“…RANKL is an osteoclast activator, which is the ligand of the receptor activator of NF-κB (RANK), and is located on the osteoclast surface. 64 When RANK binds to RANKL, the complex can stimulate and activate osteoclast differentiation. 65 RANKL/ RANK signaling regulates osteoclast formation, activation, and survival in normal bone remodeling.…”

“…However, OPG is a decoy receptor of RANKL and can inhibit bone resorption by competitively inhibiting the binding of RANKL and RANK. 64 OPG can be released from osteoblasts and protects bone from excessive resorption. The lack of balance between OPG and RANKL could result in excessive bone resorption.…”

Immunorthodontics: PD-L1, a Novel Immunomodulator in Cementoblasts, Is Regulated by HIF-1α under Hypoxia

“…Very recent in vivo investigations by Kirschneck et al (2021) demonstrated that HIF-1α from myeloid cells participates in the regulation of OIIRR. After orthodontic treatment, mice lacking HIF-1α in myeloid cells had an accelerated OTM compared to wildtype, suggesting a bone-protective activity of HIF-1α during OTM [ 25 ]. Another study also showed that the mechanotransducive stabilization of HIF-1α in PDL fibroblasts occurs under compressive forces, but not tensile forces and is regulated by phosphorylation of ERK [ 26 ].…”