Sustained hypoxia affects orthodontic tooth movement (OTM) by altering osteoclast and osteoblast differentiation, report researchers from the Institute of Science Tokyo, Japan. Hypoxic conditions resulted in reduced alveolar bone levels after OTM and lower expression of runt-related transcription factor 2 and vascular endothelial growth factor. These findings, observed in a rat model, provide critical insights into the bone remodeling process in OTM under hypoxia.

Orthodontic tooth movement (OTM) refers to the movement of a tooth due to an externally applied mechanical force. During OTM, the periodontal ligament (PDL) tissue around the tooth activates biochemical responses to recruit specific bone cells and chemical messenger molecules to aid bone remodeling. While PDL tissues are stretched on the tension side, resulting in bone deposition, orthodontic forces gradually constrict the PDL on the compression side, driving bone resorption.

Interestingly, recent reports indicate that a hypoxic environment lacking in oxygen supply is commonly observed on the compression side. Studies have demonstrated that oxygen deprivation can significantly modulate the formation of new dental bone. However, the precise mechanism by which hypoxia influences OTM and bone remodeling remains poorly understood.

To address this research gap, a team of researchers led by Professor Keiji Moriyama from the Department of Maxillofacial Orthognathics, Institute of Science Tokyo (Science Tokyo), Japan, has conducted a new study using a rat OTM model. Their research findings were published online in the journal Scientific Reports on July 1, 2025.

“Considering the relationship between hypoxia and OTM, we hypothesized that a hypoxic environment would alter the bone remodeling process,” says Moriyama, sharing valuable insights into the present study. “We utilized a closed-coil spring made of nickel-titanium to cause OTM and applied it between the right maxillary first molar and the maxillary incisors. To investigate OTM under hypoxic conditions, we housed the animals in a controlled-atmosphere chamber with an oxygen level of 10%.”

The researchers observed that animals from the hypoxia-OTM group had a higher OTM distance. Notably, the alveolar bone levels on the buccal surface in the hypoxia-OTM group were significantly reduced, indicating that hypoxia may upregulate bone resorption via osteoclast activity during OTM.

During histological examination of dental tissue, the scientists identified osteoblast cells that help form new bone, arranged along the alveolar bone on the tension side in OTM groups. However, increased osteoclastic activity was found within the PDL on the compression side.

To identify the molecular machinery and map key proteins involved in OTM under hypoxia, they utilized immunofluorescence staining. Specifically, runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF) expression in M1 periodontal tissues was assessed. Their analysis revealed that in the control-OTM group, both VEGF and RUNX2 were highly expressed on the tension side. Contrastingly, their expression on the tension side in the hypoxia-OTM group was reduced.

“RUNX2 is an important transcription factor that controls skeletal development by regulating chondrocyte and osteoblast differentiation, while VEGF promotes blood vessel formation and supports tissue growth. The lower levels of RUNX2 and VEGF on the tension side reveal that sustained hypoxia suppresses osteoblastic differentiation and limits the formation of new bone tissue after OTM,” comments Moriyama.

Taken together, this pioneering study captures the bone remodeling process in OTM under hypoxia and provides critical insights that need to be considered when treating patients with diseases accompanied by hypoxemia.