Local administration of ReveromycinA ointment suppressed alveolar bone loss in mice

• Published in: Journal of pharmacological sciences Vol. 147; no. 1; pp. 40 - 47
• Main Authors: Miyazawa, Ken, Asano, Yuichiro, Tabuchi, Masako, Kako, Shunsuke, Kawatani, Makoto, Osada, Hiroyuki, Maeda, Hatsuhiko, Goto, Shigemi
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 01.09.2021; Elsevier
• Subjects: Administration, Topical; Alveolar Bone Loss - drug therapy; Alveolar Bone Loss - prevention & control; Animals; Bone remodeling/regeneration; Bone Resorption - prevention & control; Disease Models, Animal; Drug delivery; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Ointments; Osteoclast(s); Osteoclasts - drug effects; Osteoclasts - pathology; Periodontal disease(s)/Periodontitis; Periodontal Diseases - drug therapy; Periodontal Diseases - pathology; Periodontal Diseases - prevention & control; Periodontitis - drug therapy; Periodontitis - etiology; Periodontitis - prevention & control; Pyrans - administration & dosage; Spiro Compounds - administration & dosage; Periodontal disease(s)/Periodontitis; Osteoclast(s); RMA; OPG KO; Drug delivery; WT; Bone remodeling/regeneration
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2021.05.011

ReveromycinA (RMA) was developed and is a unique agent for inhibiting osteoclast activity. In a previous study, we experimentally induced periodontal disease in a high-turnover osteoporosis osteoprotegerin-knockout mice (OPG KO) model and found that intraperitoneal administration of RMA inhibited alveolar bone resorption. We prepared a novel RMA-containing ointment for topical non-invasive administration in the oral cavity, in preparation for possible future clinical application. And we investigated whether this ointment can inhibit alveolar bone resorption in an experimental mouse model of periodontal disease. We examined wild-type (WT) and OPG KO mice ligated with wire around contact points on the left first and second molars to cause food impaction and induce experimental periodontal disease. RMA was administered three times a day. Using micro-computed tomography, we measured the volume of alveolar bone loss and also performed histological analysis. Our findings showed that localized administration of RMA containing ointment resulted in suppressed alveolar bone resorption, reduced osteoclast count, and lower immunostaining scores of inflammation sites compared with controls in both OPG KO and WT mice. Localized application of the specific osteoclast suppressor RMA in ointment form in the oral cavity could be a novel treatment for periodontitis that inhibits alveolar bone resorption locally.