Host-modulating therapeutic approaches in periodontal disease: histological evaluations
Goo, bon joon
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Periodontal disease is an oral inflammatory disease often associated with damage to the soft tissues and hard structures that support teeth. Within the subgingival biofilm, multiple microorganisms initiate inflammatory responses that can lead to a chronic oral inflammatory state, in which periodontal ligament may be damaged leading to alveolar bone loss. In recent studies, amnion-derived cellular cytokine solution (ACCS) and cytokines secreted by the amnion-derived multipotent progenitor cells (AMPs) obtained from the placenta illustrated evidence of wound healing, promotion of macrophage activity, and infected tissue repair. Furthermore, ACCS were capable of preventing periodontal inflammation induced by Porphyromonas gingivalis (P. gingivalis) in an experimental model, suggesting its role in modulating host's inflammatory response in order to arrest, if not eradicate, inflammation in periodontal tissues.. This study aimed to investigate a novel combination of ACCS that specifically targeted the bone tissues. Whereas in previous study, ACCS was tested to identify the efficacy of its ability to reduce inflammation and to repair damages in gingiva and reduce alveolar bone loss, ACCS-B was tested here to determine its impact on bone turnover. The study used a periodontal model of rabbit jaws to induce periodontitis. Periodontitis-specific pathogen P. gingivalis was applied in a carboxymethyl cellulose (CMC) slurry topically applied to the mandibular second premolars at the site of silk ligatures.. The silk ligatures were placed to serve as the retention for the P. gingivalis slurry. The protocol followed two phases, the disease induction phase (6 weeks) and the treatment phase (6 weeks). In the disease induction phase, 24 New-Zealand White rabbits were induced with topical P. gingivalis every other day on the mandibular premolars. At the end of this phase, 3 rabbits were randomly selected and sacrificed to serve as the baseline disease group. Of the remaining 21 rabbits, 3 rabbits were kept untreated and served as untreated-control group and the remaining 18 rabbits were randomly assigned to 3 different treatment groups: Placebo Treatment (Saline), ACCS-U treatment, and ACCS-B treatment. During the treatment phase, each treatment group received its respective treatments to the ligated sites 3 times a week in an every-other-day fashion. After 6 weeks, the rabbit jaws were evaluated histologically. At the end of treatment phase, the untreated group exhibited significant progression of periodontal disease evident by the destruction of soft and hard tissue on the site of interest. ACCS-U and ACCS-B showed substantial reduction of tissue inflammation and crestal bone loss compared to those in baseline disease, untreated, and saline-treated groups, however there were no statistically significant differences between ACCS-B and ACCS-Utreated sites. . Histological findings, specifically Masson's Trichrome stained sections, revealed that collagen deposition and new bone formations were actively present in the alveolar bone of ACCS-treated groups. Moreover, quantitative assessments of inflammatory cell activity and osteoclastic activity at the crestal and along the bone surfaces of the ligated sites by Hematoxylin-Eosin stains and tartrate-resistant acid phosphatase stains respectively, confirmed the anti-inflammatory activity by the ACCS-treatments. The osteocalcin stained cells also revealed the initiation of bone formation and bone repair in the ACCS-treated groups. These results state a clear indication of control of inflammatory disease and as a result, bone formation and tissue repair in both ACC-U and ACC-B treated groups.. As for the untreated group and the baseline disease group, significant disease progression is highlighted by bone loss and high level of inflammation in the site of interest. Although ACCS-B was inferior to previously tested ACCS-U with regard to anti-inflammatory effects and bone formation it clearly demonstrated its future use as potential treatment for periodontal disease, along with restoration of damaged tissues. These results further solidify findings that ACCS acts through host-modulated anti-inflammatory actions in the inflammatory conditions.