Leukemia inhibitory factor protects against experimental periodontitis through immuno‐modulations of both macrophages and periodontal ligament fibroblasts

Author:

Ou Yanjing12,Fan Le3,Wang Xiaoqi4,Xia Haibin1,Cheng Mengwen1,Huang Jing1,Liang Youde5,Wang Yining1,Zhou Yi1

Affiliation:

1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Wuhan University Wuhan Hubei PR China

2. Postdoctoral Workstation & Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology Fujian Medical University Fuzhou PR China

3. Department of Prosthodontics Guanghua School of Stomatology Hospital of Stomatology Guangdong Provincial Key Laboratory of Stomatology Sun Yat‐sen University Guangzhou Guangdong PR China

4. Department of Stomatology The First Affiliated Hospital of Soochow University Suzhou Jiangsu PR China

5. Department of Stomatology Southern University of Science and Technology Yantian Hospital Shenzhen Guangdong PR China

Abstract

AbstractBackgroundTo explore the role of leukemia inhibitory factor (LIF) in periodontitis via in vivo and in vitro experiments.MethodsThe second upper molar of LIF knockout mice and their wild‐type littermates were ligated for 8 days. Micro‐computed tomography (micro‐CT), histological analysis, and quantitative real‐time polymerase chain reaction (qRT‐PCR) were performed. The expression levels of proinflammatory cytokines were examined in mouse bone marrow derived macrophages and human periodontal ligament fibroblasts (HPDLFs) after lipopolysaccharide (LPS) treatment.ResultsLIF deficiency promoted alveolar bone loss, inflammatory cells infiltration, osteoclasts formation and collagen fiber degradation in ligature‐induced mouse, along with higher expressions of proinflammatory cytokines, including interleukin‐6 (IL6), IL‐1β (IL1B), tumor necrosis factor‐α (TNFA), matrix metalloproteinase 13 (MMP13), and RANKL/OPG ratio. Additionally, LIF deletion led to higher expression levels of these proinflammatory cytokines in mouse bone marrow‐derived macrophages from both femur and alveolar bone and HPDLFs when treated with LPS. Administration of recombined LIF attenuated TNFA, IL1B, and RANKL/OPG ratio in HPDLFs.ConclusionsThese findings indicate that LIF deficiency promotes the progress of periodontitis via modulating immuno‐inflammatory responses of macrophages and periodontal ligament fibroblasts, and the application of LIF may be an adjunctive treatment for periodontitis to resolute inflammation.

Funder

National Natural Science Foundation of China

Wuhan Science and Technology Project

Natural Science Foundation of Fujian Province

Fujian Provincial Health Technology Project

Publisher

Wiley

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