Junxiang Lian1,2, Xingwen Wu2, Yao Liu2, Wei Qiu2, Xiaofang Zhu2, Xiaoxuan Wang2, Shu Meng3, Paloma Valverde2, Bjorn Steffensen4, Qisheng Tu2, Jian Pan1, Jake Chen2,5. 1. Department of Oral & Maxillofacial Surgery, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases & Other Research Platforms, West China Hospital of Stomatology, Sichuan University, Chengdu, China. 2. Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, USA. 3. Deparment of Periodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases & Other Research Platforms, West China Hospital of Stomatology, Sichuan University, Chengdu, China. 4. Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA, USA. 5. Department of Cellular, Molecular, Developmental Biology, Tufts University School of Medicine, Boston, MA, USA.
Abstract
BACKGROUND AND OBJECTIVE: Periodontitis is a prevalent oral disease responsible for tooth loss. MicroRNAs have been proven crucial in bone disorders over the past decades. Promotive effect on osteogenic activities by microRNA-335-5p (miR-335-5p) has been well demonstrated, but its role involved in the pathogenesis of periodontitis remains elusive. In this study, we established experimental periodontitis (EP) on transgenic mice overexpressing miR-335-5p (335-Tg) to investigate the novel effects of miR-335-5p on periodontal inflammation and bone loss. METHODS: Experimental periodontitis was established via ligation. The expression of inflammatory and osteoclastic genes was examined by quantitative real-time PCR (qPCR). Morphology of alveolar bone was analyzed by microcomputed tomography (μCT). Hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Toll-like receptor 4 (TLR4) immunohistochemistry (IHC) staining were conducted for histological analysis. RESULTS: The expression of miR-335-5p decreased significantly in the periodontal tissues of EP. Compared to the WT-EP group, μCT analysis showed less bone loss in the 335-Tg-EP group accompanying with a decreased number of TRAP-positive osteoclasts. H&E and IHC staining exhibited attenuated inflammation and TLR4 expression in the 335-Tg-EP group. Furthermore, reduced expressions of IL-1β, IL-6, TNF-α, and TLR4 were also detected in the 335-Tg-EP group. Overexpression of miR-335-5p in vivo weakened the periodontal bone destruction and inflammation compared with the WT-EP group. CONCLUSIONS: Our data exhibit novel roles of miR-335-5p in preventing bone loss and inflammation in experimental periodontitis.
BACKGROUND AND OBJECTIVE:Periodontitis is a prevalent oral disease responsible for tooth loss. MicroRNAs have been proven crucial in bone disorders over the past decades. Promotive effect on osteogenic activities by microRNA-335-5p (miR-335-5p) has been well demonstrated, but its role involved in the pathogenesis of periodontitis remains elusive. In this study, we established experimental periodontitis (EP) on transgenic mice overexpressing miR-335-5p (335-Tg) to investigate the novel effects of miR-335-5p on periodontal inflammation and bone loss. METHODS: Experimental periodontitis was established via ligation. The expression of inflammatory and osteoclastic genes was examined by quantitative real-time PCR (qPCR). Morphology of alveolar bone was analyzed by microcomputed tomography (μCT). Hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Toll-like receptor 4 (TLR4) immunohistochemistry (IHC) staining were conducted for histological analysis. RESULTS: The expression of miR-335-5p decreased significantly in the periodontal tissues of EP. Compared to the WT-EP group, μCT analysis showed less bone loss in the 335-Tg-EP group accompanying with a decreased number of TRAP-positive osteoclasts. H&E and IHC staining exhibited attenuated inflammation and TLR4 expression in the 335-Tg-EP group. Furthermore, reduced expressions of IL-1β, IL-6, TNF-α, and TLR4 were also detected in the 335-Tg-EP group. Overexpression of miR-335-5p in vivo weakened the periodontal bone destruction and inflammation compared with the WT-EP group. CONCLUSIONS: Our data exhibit novel roles of miR-335-5p in preventing bone loss and inflammation in experimental periodontitis.
Authors: Jane B Lian; Gary S Stein; Andre J van Wijnen; Janet L Stein; Mohammad Q Hassan; Tripti Gaur; Ying Zhang Journal: Nat Rev Endocrinol Date: 2012-01-31 Impact factor: 43.330