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

Objective:  To investigate the isolated and combined effects of compression and hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs). Materials and Methods:  A periodontal ligament tissue model (PDLtm) was established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co-glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for 6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used for gene expression analysis. The conditioned media were used for the coculture of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase staining was done to examine OC formation. Results:  Either compression or hypoxia alone significantly up-regulated the gene expression of pro-osteoclastogenic cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the combination of the two had significantly stronger effects than either stimulation alone. In addition, comparing the two stimulants, we found that the osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the compression group than in the hypoxia group (at 24 hours). Conclusions:  Both compressive force and hypoxia may take part in initiating osteoclastogenesis in orthodontic tooth movement and may have combinatory effects, which could update our concepts of the mechanisms involved in the initiation of bone resorption on the pressure side of the tooth in question.