AUTHOR=Li Dengke , Zhang Wuyang , Ye Weiliang , Liu Yuan , Li Yuan , Wang Yiming , Shi Bingqing , Zheng Xueni , An Ying , Ma Zhen , Hu Kaijin , Zhou Hongzhi , Xue Yang TITLE=A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1046451 DOI=10.3389/fphar.2022.1046451 ISSN=1663-9812 ABSTRACT=

The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled “host-modulation therapy,” has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugated tetracycline with odanacatib (a selective inhibitor of cathepsin K) to construct a multifunctional drug (TC-ODN). We discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. In vivo, TC-ODN could be absorbed and distributed specifically to the bone after systemic administration, and accumulation of TC-ODN increased bone mineral density in ovariectomized rats. Importantly, periodontal administration of TC-ODN could successfully promote bone healing in periodontitis rats with alveolar bone loss. The findings in our study uncovered the excellent biocompatibility and multifunction of TC-ODN, including bone-targeted accumulation, immunoregulation, anti-inflammatory activity and promotion of bone healing, which might contribute to the clinical treatment of periodontitis.