The role of HIF-1α in nicotine-induced root and bone resorption during orthodontic tooth movement

Abstract

Summary Background In orthodontic tooth movement (OTM), pseudo-inflammatory processes occur that are similar to those of nicotine-induced periodontitis. Previous studies have shown that nicotine accelerates OTM, but induces periodontal bone loss and dental root resorption via synergistically increased osteoclastogenesis. This study aimed to investigate the role of hypoxia-inducible factor 1 alpha (HIF-1α) in nicotine-induced osteoclastogenesis during OTM. Materials/Methods Male Fischer-344 rats were treated with l-Nicotine (1.89 mg/kg/day s.c., N = 10) or NaCl solution (N = 10). After a week of premedication, a NiTi spring was inserted to mesialize the first upper left molar. The extent of dental root resorption, osteoclastogenesis, and HIF-1α protein expression was determined by (immuno)histology, as well as bone volume (BV/TV) and trabecular thickness (TbTh) using µCT. Receptor activator of nuclear factor of activated B-cells ligand (RANK-L), osteoprotegerin (OPG), and HIF-1α expression were examined at the protein level in periodontal ligament fibroblasts (PDLF) exposed to pressure, nicotine and/or hypoxia, as well as PDLF-induced osteoclastogenesis in co-culture experiments with osteoclast progenitor cells. Results Nicotine favoured dental root resorptions and osteoclastogenesis during OTM, while BV/TV and TbTh were only influenced by force. This nicotine-induced increase does not appear to be mediated by HIF-1α, since HIF-1α was stabilized by force application and hypoxia, but not by nicotine. The in vitro data showed that the hypoxia-induced increase in RANK-L/OPG expression ratio and PDLF-mediated osteoclastogenesis was less pronounced than the nicotine-induced increase. Conclusions Study results indicate that the nicotine-induced increase in osteoclastogenesis and periodontal bone resorption during OTM may not be mediated by hypoxic effects or HIF-1α stabilization in the context of nicotine-induced vasoconstriction, but rather by an alternative mechanism.

The Synergistic Effect of Nicotine and Staphylococcus aureus on Peri-Implant Infections

“…Most scholars believed that cigarette smoking had a negative influence on bone healing while nicotine alone did not have such effect ( Stefani et al, 2002 ; Cesar-Neto et al, 2003 ; Giorgetti et al, 2010 ; Zhu et al, 2020 ). However, nicotine administrated alone was reported to induce the osteoclastogenesis in another study ( Ullrich et al, 2020 ). In our study, nicotine administrated alone induced few osteolysis and no significant difference was observed between the nicotine and control groups.…”

“…Ti rods with PBS and Ti rods with S. aureus were implanted into the left femurs of the rats as previously described ( Diefenbeck et al, 2016 ; Nie et al, 2017 ). Then, ten randomly assigned rats from each group were subcutaneously injected with nicotine (2 mg/kg) once a day ( Milovanovic et al, 2018 ; Ullrich et al, 2020 ), and the other ten were injected with PBS as control. There were four groups in total: PBS as the control group, S. aureus group, nicotine group, and S. aureus -nicotine combination group.…”

Local Vascularization during Orthodontic Tooth Movement in a Split Mouth Rat Model—A MRI Study

“…We defined termination criteria and monitored animal welfare daily. The rats were kept in a conventional animal laboratory at the University of Erlangen-Nuremberg (Preclinical Experimental Animal Centre PETZ) and had free access to a standard rat diet (V1535, ssniff, Soest, Germany) and to tap water [23][24][25]. Four days after onset of tooth movement and after MRI measurements, rats were killed according to legal guidelines.…”

“…After twelve days of acclimatization, rats were narcotized by injection of 6 mg xylazine and 90 mg ketamine per kg body weight [23,[25][26][27]. An orthodontic elastic band (774-200-01, Dentaurum, Ispringen, Germany) was inserted in the approximal space between the first and the second left molar of the rat upper jaw for four days [25], whereas the contralateral jaw side remained untreated.…”

“…They were split into control and orthodontically treated sides. Afterwards, they incubated in 10% Tris-buffered ethylene diamine tetra-acetic solution (pH 7.4) at room temperature for eight weeks to demineralize the alveolar bone [23][24][25]. Both sides were embedded in paraffin and cut in sagittal-oblique sections of 5 µm with a rotating microtome (HM350, Microm International, Dreieich, Germany).…”