The Role of Hypoxia in Orthodontic Tooth Movement

Abstract

Orthodontic forces are known to have various effects on the alveolar process, such as cell deformation, inflammation, and circulatory disturbances. Each of these conditions affecting cell differentiation, cell repair, and cell migration, is driven by numerous molecular and inflammatory mediators. As a result, bone remodeling is induced, facilitating orthodontic tooth movement. However, orthodontic forces not only have cellular effects but also induce vascular changes. Orthodontic forces are known to occlude periodontal ligament vessels on the pressure side of the dental root, decreasing the blood perfusion of the tissue. This condition is accompanied by hypoxia, which is known to either affect cell proliferation or induce apoptosis, depending on the oxygen gradient. Because upregulated tissue proliferation rates are often accompanied by angiogenesis, hypoxia may be assumed to fundamentally contribute to bone remodeling processes during orthodontic treatment.

The increased number of osteoblasts and capillaries in orthodontic tooth movement post-administration of Robusta coffee extract

“…Cells then respond to hypoxia by expressing cellular mediators, especially hypoxia-inducible factor 1 (HIF-1) that can promote angiogenesis, stimulate cell proliferation, and prevent cell death. 9 Moreover, hypoxia induces the formation of an active transcription factor HIF-1 and activates genes that encode endhothelial vascular growth factor (VEGF) 9 known as one of the most important mitogens to induce angiogenesis. 10 Angiogenesis is the growth of new blood vessels from existing ones.…”

“…12 Matrix metalloproteinase (MMP) is also important for angiogenesis because of its role in extracellular matrix degradation, resulting in the migration of endothelial cells. 9 MMP-2 is even considered a direct transcriptional target of HIF-1α, mediating endothelial cell migration in response to hypoxia. 13 In general, VEGF expression is detected in osteoblasts, osteocytes, and fibroblasts at the tension site after 10 days of orthodontic tooth movement.…”

Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

“…This difference might be caused by the up-regulation of VEGF in that it could partially act as a macrophage colony-stimulating factor, 21 and the RANKL expression in OBs induced by COX-2(PGE 2 )/IL-1. 26,27 However, compression and hypoxia act in a magnitude-dependent manner, 29,30 while the adopted interventions in the present study (compression of 25 g/cm 2 and 2% O 2 ) may not be proportional to the in vivo environment, which should be further clarified.…”

“…To simulate the compressed PDL under orthodontic force, a modified weight method was used as previously described. 5,13 Briefly, a cover glass was placed over each PDLtm, then a glass bottle with lead granules having a total weight of 100 g was placed on the cover glass to produce a mechanical force of 25 g/cm 2 . To induce hypoxia, the PDLtm was cultured in an incubator with an atmosphere of 2% O 2 .…”

“…When a tooth is subjected to orthodontic force, numerous changes occur in the alveolar bone and periodontium, among which mechanical force and hypoxia have been the most studied and described to regulate bone remodeling. 1,2 The role of mechanical compression in promoting periodontal ligament (PDL)-induced osteoclastogenesis has been reported by numerous studies. [3][4][5][6] Briefly, when subjected to a compressive force, the periodontal ligament cells (PDLCs) elicit osteoclast (OC) formation through regulating the expression of related agents, including receptor activator for nuclear factor-k B ligand (RANKL) expression and osteoprotegerin (OPG).…”