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Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis
Affiliation:1. Department of Oral and Maxillofacial Pathobiology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan;2. Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan;3. R&D Division, Sunstar Inc, Osaka, Japan;4. Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima, Japan;1. School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, China;2. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an, Shaanxi, China;1. Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD, USA;2. Preventive Dental Sciences Department, School of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia;1. Neuroscience Institute, Miguel Hernandez University (UMH-CSIC), San Juan, Alicante, Spain;2. School of Dentistry, Faculty of Medicine, University of Murcia, Murcia, Spain;3. Hematology Department, Hematopoietic Transplant and Cellular Therapy Unit, Virgen de la Arrixaca Clinical University Hospital, IMIB-Arrixaca, University of Murcia, Spain;4. IMIB-Arrixaca and Centro de Investigación Biomédica en Red en el Área de Salud Mental (CIBERSAM), University of Murcia, Murcia, Spain;1. Department of Endodontology, Restorative Dental Sciences, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China;2. Department of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China;3. Department of Biomaterials and Biomechanics, School of Dentistry Center for Regenerative Medicine, Oregon Health and Science University, Portland, Oregon
Abstract:BackgroundControl of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it.MethodsWe examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system.ResultsBoth CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation.ConclusionsbLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.
Keywords:Anti-inflammatory agents  Osteoblast(s)  Periodontitis  Cytokine(s)  Bone biology  Lactoferrin
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