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DNA methylation profiling in different phases of temporomandibular joint osteoarthritis in rats
Institution:1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, PR China;2. Center for Temporomandibular Joint Disorder and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing 100081, PR China;3. Department of Dermatology and Venereology, Peking University First Hospital, Beijing 100034, PR China;4. Department of Biochemistry and Molecular Biology, Peking University School of Basic Medical Sciences, Beijing 100191, PR China;1. Graduate student, Division of Reconstructive Surgery for the Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences; Research Fellow of the Japan Society for the Promotion of Science, Niigata, Japan;2. Professor, Division of Reconstructive Surgery for the Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;3. Associate Professor, Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;4. Professor, Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;5. Assistant Professor, Division of Reconstructive Surgery for the Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;6. Professor, Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;7. Emeritus Professor, Division of Reconstructive Surgery for the Oral and Maxillofacial Region, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan;1. Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China;2. University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China;3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China;4. CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China;5. Suplead Co., LTD, Building D, 389 Ruoshui Road, Suzhou, 215000, China;6. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, China;7. College of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan, 467036, China;8. School of Life Science and Technology, ShanghaiTech University, Shanghai, 200031, China;1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China;2. Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China;3. Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China;4. Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China;1. Doctoral Candidate, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning Province, China;2. Lecturer, Department of Oral Anatomy and Physiology, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning Province, China;3. Doctoral Candidate, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning Province, China;1. Worldwide Medicinal Chemistry, Pfizer, 610 Main Street, Cambridge, MA 02139, USA;2. The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA;3. Neuroscience and Pain Research Unit, Pfizer, 610 Main Street, Cambridge, MA 02139, USA;4. Worldwide Medicinal Chemistry, Pfizer, Eastern Point Road, Groton, CT 06340, USA;5. Structural Biology and Biophysics, Worldwide Medicinal Chemistry, Pfizer, Eastern Point Road, Groton, CT 06340, USA;6. Primary Pharmacology Group, Pfizer, Eastern Point Road, Groton, CT 06340, USA;7. Rare Disease Research Unit, Pfizer, 610 Main Street, Cambridge, MA 02139, USA;1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China;2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
Abstract:ObjectiveTemporomandibular joint osteoarthritis (TMJOA) is a complex disease with strong genetic and epigenetic components in its pathogenesis. The aim of this study was to evaluate DNA methylation in mandibular head cartilage in different phases of experimentally-induced TMJOA in rats.DesignDNA methylation was evaluated using microarrays in the mandibular head cartilage of early, intermediate and late stage experimentally-induced TMJOA, and of the normal age-matched control groups. Genes with differentially methylated CpG sites were analyzed to reveal the over-represented gene ontologies and pathways at different stages, and were compared with published expression profiles to assess their overlappings. The DNA methylation patterns of the target genes were validated by methylated DNA immunoprecipitation qPCR in additional independent cartilage samples and mRNA levels were analyzed by real-time PCR.ResultsWe observed 9489 differentially methylated regions between the TMJOA and controls. A total of 440 consistently altered genes were revealed in all three stages; most (80%) were hypomethylated and many were associated with cell cycle regulation. We also detected different DNA methylation changes in early and late stage TMJOA (Rearly = 0.68, Rlate = 0.47), while the differences between age-matched healthy cartilage were subtle. Strong inverse changes between methylation status and mRNA levels were confirmed in Adamts5, Chad, Cldn11 and Tnf.ConclusionsOur data reveals dynamic DNA methylation patterns during the progression of TMJOA, with a different host of genes and pathways. The changes of cartilage DNA methylation patterns might contribute to understand the etiologic mechanisms of TMJOA epigenetically.
Keywords:Temporomandibular joint  Osteoarthritis  DNA methylation  Claudin11
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