Abstract
Osteoclastic bone resorption enables orthodontic tooth movement (OTM) in orthodontic treatment. Previously, we demonstrated that local epigallocatechin gallate (EGCG) injection successfully slowed the rate of OTM; however, repeat injections were required. In the present study, we produced a liquid form of EGCG-modified gelatin (EGCG-GL) and examined the properties of EGCG-GL with respect to prolonging EGCG release, NF-E2-related factor 2 (Nrf2) activation, osteoclastogenesis inhibition, bone destruction, and OTM. We found EGCG-GL both prolonged the release of EGCG and induced the expression of antioxidant enzyme genes, such as heme oxygenase 1 (Hmox1) and glutamate-cysteine ligase (Gclc), in the mouse macrophage cell line, RAW264.7. EGCG-GL attenuated intracellular reactive oxygen species (ROS) levels were induced by the receptor activator of nuclear factor-kB ligand (RANKL) and inhibited RANKL-mediated osteoclastogenesis in vitro. An animal model of bone destruction, induced by repeat Lipopolysaccharide (LPS)-injections into the calvaria of male BALB/c mice, revealed that a single injection of EGCG-GL on day-1 could successfully inhibit LPS-mediated bone destruction. Additionally, experimental OTM of maxillary first molars in male mice was attenuated by a single EGCG-GL injection on day-1. In conclusion, EGCG-GL prolongs the release of EGCG and inhibits osteoclastogenesis via the attenuation of intracellular ROS signaling through the increased expression of antioxidant enzymes. These results indicate EGCG-GL would be a beneficial therapeutic approach both in destructive bone disease and in controlling alveolar bone metabolism.
Highlights
Osteoclasts are multi-nucleated cells that can resorb bone tissue [1]
A single injection of epigallocatechin gallate (EGCG)-GL significantly reduced the number of osteoclasts on the alveolar bone surface relative to controls, see Figure 8c,d. These results suggest that a single injection of EGCG-modified gelatin (EGCG-GL) inhibits osteoclastogenesis, and thereby attenuates orthodontic tooth movement (OTM)
We previously reported that repeated local injections of EGCG solution inhibited osteoclastogenesis, and retards OTM [21]
Summary
Osteoclasts are multi-nucleated cells that can resorb bone tissue [1] They are tightly regulated by the receptor activator of nuclear factor-kB ligand (RANKL) [2]. Osteoprotegerin (OPG), a decoy receptor for RANKL, can negatively regulate OTM where local delivery of OPG [17] and localized OPG-gene induction by gene transfer [18] inhibits OTM. This local gene transfer is an effective way to control the rate of OTM, it is difficult to apply clinically. EGCG can induce Nrf2-mediated anti-oxidation and ROS scavenging, and inhibit the rate of OTM [21]. EGCG-GL and confirmed that a single injection of EGCG-GL could inhibit osteoclastogenesis in vivo
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