**11. Animal studies: the amelioration of ligature-induced PD by RES**

Although microbial dysbiosis is a necessary early occurrence in the pathogenesis of PD, the resulting chronic inflammation is the causal factor regarding its progression and continuous tissue destruction [106, 107]. Therefore, an effective therapeutic approach for the mitigation of PD would be to address the pathogenetically deregulated inflammatory pathways, mediators, and markers, encouraging the system to return to balance without deleterious side effects.

In a commonly used animal model, PD is induced by fitting a ligature around the neck of pre-selected molar teeth. Typically, PD that is induced in this way predictably presents with significant alveolar bone loss, accompanied by the increased expression of pro-inflammatory genes such as those for IL-1β, IL-6, and TNF-α. Notably, increased mRNA expression of genes coding for osteoclastogenic proteins and receptor activator of nuclear factor-k B ligand (RANKL) has also been reported when applying this model [108].

Morphometric analysis [27, 100, 101, 103, 109–111] and/or Micro-CT [104, 112–114] has been employed to demonstrate that RES reduced the alveolar bone loss from experimentally induced PD. The micro-CT analyses also reported improved bone density, suggesting that at the very least, RES has therapeutic potential as an adjunct to traditional SRP. This of course is caveated by emphasising the dependence of this data on the relevance of the PD animal model, and the need for validation with human studies.
