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Porphyromonas gingivalis LPS inhibits osteoblastic differentiation and promotes pro-inflammatory cytokine production in human periodontal ligament stem cells
Affiliation:1. Department of Oral Pathology, Osaka Dental University, Osaka, Japan;2. Department of Periodontology, Osaka Dental University, Osaka, Japan;1. State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, Xi’an 710032, PR China;2. State Key Laboratory of Military Stomatology, Department of VIP Dental Care, School of Stomatology, The Fourth Military Medical University, Xi’an 710032, PR China;3. NingXia People''s Hospital, Department of Stomatology, NingXia, Yinchuan 750021, PR China;4. Oral Biology, School of Dentistry, University of Birmingham, B4 6NN, UK;1. Oral Health Science Center, Tokyo Dental College, 1-2-2, Masago, Mihama-ku, Chiba 261-8502, Japan;2. Department of Clinical Pathophysiology, Tokyo Dental College, 1-2-2, Masago, Mihama-ku, Chiba 261-8502, Japan;3. Department of Microbiology, Tokyo Dental College, 1-2-2, Masago, Mihama-ku, Chiba 261-8502, Japan;1. Department of Stomatology, The Affiliated School of Clinical Medicine of Xuzhou Medical College, Xuzhou Central Hospital, Xuzhou, China;2. Department of Urology, The Affiliated School of Clinical Medicine of Xuzhou Medical College, Xuzhou Central Hospital, Xuzhou, China;1. Department of Periodontology, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, PR China;2. Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing 100191, China;1. Department of Conservation Dentistry and Endodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, PR China;2. Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, PR China
Abstract:ObjectivePorphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) induces pro-inflammatory cytokines, such as interleukin-1 β (IL-1β), IL-6, and IL-8, which induce periodontal tissue destruction. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration and are expected to have future applications in cellular therapies for periodontitis. However, no studies have examined the effects of P. gingivalis LPS on PDLSCs. The aim of this study was to investigate how P. gingivalis LPS affects the osteoblastic differentiation and pro-inflammatory cytokine production of PDLSCs.DesignPDLSCs were obtained from healthy adult human mandibular third molars. The identification of PDLSCs was confirmed by immunohistochemical evaluations of the mesenchymal stem cell markers STRO-1 and SSEA-4. Cell proliferation and osteoblastic differentiation were investigated by culturing the PDLSCs in a normal or osteogenic medium with P. gingivalis LPS (0, 1, or 10 μg/mL) and then measuring the alkaline phosphatase (ALP) activity and the production of collagen type 1 Alpha 1 (COL1A1), osteocalcin production, and mineralisation. Additionally, we examined the production of IL-1β, IL-6, and IL-8 in the PDLSCs.ResultsP. gingivalis LPS inhibited the ALP activity, COL1A1 and osteocalcin production, and mineralisation in the PDLSCs, which are positive for STRO-1 and SSEA-4. P. gingivalis LPS also promoted cell proliferation and produced IL-1β, IL-6, and IL-8.ConclusionsThis study provides the first findings that P. gingivalis LPS inhibits osteoblastic differentiation and induces pro-inflammatory cytokines in PDLSCs. These findings will help clarify the relationship between periodontitis and periodontal tissue regeneration.
Keywords:Periodontal ligament  Stem cells  Lipopolysaccharides  Osteoblasts  Cell differentiation  Cytokines
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