Maki Nakagawa1, Michihiro Shirasugi2, Toshiro Yamamoto3, Takaaki Nakaya4, Narisato Kanamura3. 1. Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 2. Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Dentistry and Oral Surgery, Mitsubishi Kyoto Hospital, Kyoto, Japan. 3. Department of Dental Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 4. Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: tnakaya@koto.kpu-m.ac.jp.
Abstract
OBJECTIVE: The purpose of this study was to clarify the relationship between bacteria-induced butyric acid and periodontal disease progression. DESIGN: Normal human gingival fibroblasts were exposed to butyric acid (0, 1, 5, 10, and 15 mM) adjusted to a pH of 7.2-7.4 using sodium hydroxide for 0-96 h and cell viability was evaluated. In addition, the effects of butyric acid on the production of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in gingival fibroblasts were analyzed by real-time RT-PCR, ELISA, western blotting, and stromelysin zymography. RESULTS: Butyric acid reduced the viability of gingival fibroblasts in a concentration- and time-dependent manner. Furthermore, butyric acid promoted production of MMP-1, MMP-3, and MMP-10 in gingival fibroblasts and suppressed TIMP-2 protein production. CONCLUSIONS: Butyric acid promoted overproduction of MMPs, resulting in a disruption of the balance between MMPs and TIMPs expression in gingival fibroblasts. Our study suggests that the butyric acid produced by causative bacteria stimulates excessive MMP expression in periodontal tissue, leading to destruction of the tissue.
OBJECTIVE: The purpose of this study was to clarify the relationship between bacteria-induced butyric acid and periodontal disease progression. DESIGN: Normal human gingival fibroblasts were exposed to butyric acid (0, 1, 5, 10, and 15 mM) adjusted to a pH of 7.2-7.4 using sodium hydroxide for 0-96 h and cell viability was evaluated. In addition, the effects of butyric acid on the production of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in gingival fibroblasts were analyzed by real-time RT-PCR, ELISA, western blotting, and stromelysin zymography. RESULTS:Butyric acid reduced the viability of gingival fibroblasts in a concentration- and time-dependent manner. Furthermore, butyric acid promoted production of MMP-1, MMP-3, and MMP-10 in gingival fibroblasts and suppressed TIMP-2 protein production. CONCLUSIONS:Butyric acid promoted overproduction of MMPs, resulting in a disruption of the balance between MMPs and TIMPs expression in gingival fibroblasts. Our study suggests that the butyric acid produced by causative bacteria stimulates excessive MMP expression in periodontal tissue, leading to destruction of the tissue.