Effects of green tea extract epigallocatechin-3-gallate (EGCG) on orthodontic tooth movement and root resorption in rats

Upon orthodontic forces, remodeling of the periodontium occurs, which in turn generates orthodontic tooth movement (OTM). It is a complex biological process involving bone resorption on the pressure side, and bone neogenesis on the tension side, mediated respectively by osteoclasts and osteoblasts (Rygh, 1976, Storey, 1973).

Orthodontic induced root resorption (OIRR), known as one of the most common complications in orthodontic treatment, receives extensive attention from clinical orthodontists, and is unpredictable and unavoidable (Harry and Sims, 1982, McLaughlin, 1964, Stenvik and Mjor, 1970). Studies have shown that the main functional cells involved in root resorption (cementoclasts) share morphological similarities with those involved in alveolar bone resorption (osteoclasts), and both processes involve the same ligand receiving system RANK/RANKL (Arana-Chavez and Bradaschia-Correa, 2009, Sasaki, 2003, Yamaguchi, 2009).

Tea, a time-honored beverage obtained from the leaves of Camellia sinensis (L.) Kuntze, is now one of the most popular drinks worldwide (Hayat et al., 2015). With an annual consumption of 3 billion kg, tea occupies the second place in all kinds of beverages, second only to water (Liao et al., 2001, Shen et al., 2009, Velayutham et al., 2008). To date, tea has already been confirmed to have a veriaty of beneficial health characteristics, such as anti-hypertension, anti-cancer, anti- inflammation, etc (Hayakawa et al., 2019, Suzuki et al., 2016). And as an independent factor, the amount of tea drinking was proved to be positively correlated with bone mineral density at femur and lumbar vertebrae (Zhang et al., 2017). Kaboosaya has also confirmed that drinking green tea alleviates alveolar bone resorption in ligature induced periodontitis in mice (Kaboosaya et al., 2020).

The main functional components of tea are polyphenols, while more than 80% of them are catechins, which are composed of epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG) and epicatechin (EC). Among all these tea polyphenols, EGCG holds the highest content (more than 50%) and strongest biological activity (Haratifar and Corredig, 2014, Liao et al., 2020, Mah et al., 2014). EGCG possesses strong free radical scavenging activity, which is endowed by its polyhydroxy structure, laying the foundation of its good anti-oxidant, anti-virus, and anti-inflammatory effects (Chakrawarti et al., 2016).

Furthermore, it has been convinced that EGCG can participate in the regulation of bone metabolism in a variety of direct or indirect ways and positively regulate bone remodeling (Tominari et al., 2015, Yagi et al., 2013). For example, EGCG is able to play a pro osteogenic role by counteracting the inhibition of H2O2 on osteogenic differentiation of BMSCs, and this effect may be related to Wnt/β-catenin pathway. (Wang et al., 2016). EGCG was also confirmed to significantly promote the osteogenic differentiation of human alveolar bone osteoblasts (but had no significant effect on their proliferation) through the PI3K / Akt signaling pathway, elevate ALP activity and promote the formation of mineralized nodules, and increase the expression of related genes in this process (Ding et al., 2021). And ALP is an early marker of osteoblast differentiation (Liu et al., 2014). For osteoclasts, EGCG is able to act on nuclear factor κB. Significantly inhibits osteoclast differentiation and bone resorption activity in the early stages of cell generation (Lin et al., 2009). Moreover, EGCG can effectively inhibit the bone resorption process by inhibiting the gene expression and enzyme activity of metalloproteinases in osteoclasts (Oka et al., 2012, Yun et al., 2004).

It is widely accepted that substances capable of regulating bone metabolism may also affect periodontal remodeling during orthodontics. However, it was found that current research on this area has rarely been reported. One subject group has done the exploration of related aspects (Katsumata et al., 2018), and suggested that application of EGCG was able to reduce OTM. This experiment focused more on the enhancement of EGCG inhibitory osteoclastic potency after material modification. The effect of EGCG on OTM was only briefly presented as a small part of the overall experiment. While for periodontal tissue remodeling during orthodontic tooth movement as well as root resorption status, the authors did not systematically explore them.

We speculate that EGCG may promote periodontal tissue neogenesis during orthodontics in rats and may reduce OIRR during this process. To verify this speculation and preliminarily explore the related mechanism, we performed the present experiment.

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