Osteocytes play an important role in experimental periodontitis in healthy and diabetic mice through expression of RANKL

Journal of Clinical Periodontology - Tập 45 Số 3 - Trang 285-292 - 2018
Dana T. Graves1, Ahmed Alshabab2,1, Mayra Laino Albiero1,3, Marcelo Mattos1, Jôice Dias Corrêa1,4, Shanshan Chen1,5, Yang Yang1,5
1Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
2Department of Periodontics, Faculty of Dentistry, Najran University, Najran, Saudi Arabia
3Department of Periodontics, State University of Campinas, Piracicaba, Brazil
4School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, Brazil
5State Key Laboratory of Oral Disease, West China Hospital of Stomatology Sichuan University, Chengdu, Sichuan, China

Tóm tắt

AbstractAimPeriodontitis results from bacteria‐induced inflammation. A key cytokine, RANKL, is produced by a number of cell types. The cellular source of RANKL critical for periodontitis has not been established.MethodsWe induced periodontal bone loss by oral inoculation of Porphyromonas gingivalis and Fusobacterium nucleatum in both normoglycaemic and streptozotocin‐induced type 1 diabetic mice. Experimental transgenic mice had osteocyte‐specific deletion of floxed receptor activator of nuclear factor kappa‐B ligand (RANKL) mediated by DMP‐1‐driven Cre recombinase. Outcomes were assessed by micro‐CT, histomorphometric analysis, immunofluorescent analysis of RANKL and tartrate‐resistant acid phosphatase staining for osteoclasts and osteoclast activity.ResultsOral infection stimulated RANKL expression in osteocytes of wild‐type mice, which was increased by diabetes and blocked in transgenic mice. Infected wild‐type mice had significant bone loss and increased osteoclast numbers and activity, which were further enhanced by diabetes. No bone loss or increase in osteoclastogenesis or activity was detected in transgenic mice with RANKL deletion in osteocytes that were normoglycaemic or diabetic.ConclusionsThis study demonstrates for the first time the essential role of osteocytes in bacteria‐induced periodontal bone loss and in diabetes‐enhanced periodontitis.

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Tài liệu tham khảo

10.1359/jbmr.1997.12.12.2040

10.1902/jop.2015.140520

10.1359/jbmr.2002.17.10.1822

10.1038/ng1905

10.1002/jbmr.2096

George A., 1993, Characterization of a novel dentin matrix acidic phosphoprotein. Implications for induction of biomineralization, Journal of Biological Chemistry, 268, 12624, 10.1016/S0021-9258(18)31434-0

10.1177/00220345590380062001

10.1902/jop.1998.69.12.1419

10.1159/000329675

10.4161/21505594.2014.990806

10.1016/j.bone.2015.02.011

10.1128/IAI.06371-11

10.4049/jimmunol.1601114

10.2353/ajpath.2006.060180

10.1016/j.bone.2012.01.025

10.11005/jbm.2014.21.1.55

Lin X., 2010, Antibody to RANKL Ameliorates T cell‐mediated Periodontal Bone Resorption, Infection and Immunity

Liu D., 2003, Expression of RANKL and OPG mRNA in periodontal disease: Possible involvement in bone destruction, International Journal of Molecular Medicine, 11, 17

10.1177/154405910708600404

10.1111/j.0022-202X.2004.22711.x

10.1038/nm.2452

O'Brien C. A., 2012, Osteocyte control of osteoclastogenesis, Bone, 54, 258, 10.1016/j.bone.2012.08.121

10.1016/j.ajpath.2013.08.017

10.1096/fj.11-196279

10.1038/srep16694

10.1111/j.1600-051X.2009.01393.x

10.1902/jop.2011.100643

10.1111/j.1600-0765.1981.tb00945.x

10.1177/0022034515625962

10.1038/ijos.2015.2

10.1016/j.ajpath.2014.12.006

10.1159/000351896

Xiao E., 2017, Diabetes Enhances IL‐17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity, Cell Host & Microbe, 22, e124

10.1038/nm.2448

10.2337/db14-0589

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Thông tin xuất bản

Journal of Clinical Periodontology

Tập 45 Số 3

285-292

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