Clinical implications of macrophage dysfunction in the development of osteoarthritis of the knee |
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| Affiliation: | 1. Department of Orthopaedics Surgery, Laboratory of Endocrinology and Metabolism, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China;2. Department of Orthopaedics Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;3. Laboratory of Endocrinology and Metabolism, Department of Endocrinology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;4. Core Facility of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China;1. Department of Biomedical Sciences, University of Padova, Via Bassi 58, I-35131 Padova, Italy;2. Centre for Mechanics of Biological Materials, University of Padova, Via A. Gabelli 65, 35127 Padova, Italy;3. Department of Industrial Engineering, University of Padova, Via Venezia 1, I-35131 Padova, Italy;4. Rheumatology Unit, Department of Medicine − DIMED, University Padova, 35128 Padova, Italy;5. Musculoskeletal Pathology and Oncology Laboratory, Department of Orthopedics and Orthopedic Oncology, 35128 University of Padova, Italy;6. Clinica Medica 3, Department of Medicine − DIMED, University of Padova, 35128 Padova, Italy;7. RAMSES Laboratory, RIT Department, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy;8. Department. of Pediatric Orthopedics and Traumatology, IRCCS Istituto Ortopedico Rizzoli Bologna, Italy;9. Department of Orthopedics and Orthopedic Oncology, 35128 University of Padova, Italy;10. Institute of Human Anatomy, Department of Neuroscience, University of Padova, Via A. Gabelli 65, 35127 Padova, Italy;2. Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA;3. Department of Medicine, Duke University School of Medicine, Durham, NC, USA;4. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA;6. Division of Nuclear Medicine, Department of Radiology, Duke University School of Medicine, Durham, NC, USA;5. Department of Radiology, The Medical Physics Program and Nuclear Medicine, Duke University School of Medicine, Durham, NC, USA;11. Eli Lilly and Company, Indianapolis, IN, USA;1. Fourth Department of Orthopaedics & Trauma, ‘KAT’ General Hospital, Kifissia, 14561 Athens, Greece;2. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street, 11527 Athens, Greece;2. Department of Orthopaedics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;3. Department of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;4. Medtronic-Sofradim Production, Trévoux, France |
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| Abstract: | Osteoarthritis (OA) is the most common form of arthritic disease, leading to disability and impaired quality of life and no curative treatments exist. Increasing evidence indicates that low-grade inflammation plays a pivotal role in the onset and progression of OA. In this review, we summarize emerging findings on the pathological roles of synovial macrophages, adipose tissue macrophages, and osteoclasts in OA and their potential clinical implications from cell biology to preclinical and preliminary clinical trials. The failure of synovial macrophages to transition from pro-inflammatory M1 to anti-inflammatory M2 subtypes may contribute to the initiation and maintenance of synovitis in OA. M1 macrophages promote the inflammatory microenvironment and progression of OA through interactions with synovial fibroblasts and chondrocytes, thus increasing the secretion of matrix metalloproteinases. Direct inhibition of M1 or promotion of M2 polarization may be useful therapeutic interventions. Adipose tissue macrophages present in the infrapatella fat pad (IPFP) were involved in the progression of obesity-induced OA, which contributed to changes in the integrity of the IPFP. Furthermore, macrophages and osteoclasts in the subchondral bone were involved in bone remodeling and pain through uncoupled osteoclast/osteoblast activity and increased nociceptive signaling. Growing evidence has indicated an important role for macrophage-mediated low-grade inflammation in OA. Fully understanding the link between macrophages and other cells in joints will provide new insights into OA disease modification. |
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| Keywords: | Osteoarthritis Inflammation Immunity Macrophage |
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