Primary human chondrocytes respond to compression with phosphoproteomic signatures that include microtubule activation |
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| Affiliation: | 1. Department of Mechanical & Industrial Engineering, Montana State University, United States;2. Department of Chemistry and Biochemistry, Montana State University, United States;1. Centre for Exercise and Rehabilitation Science and The Institute for Lung Health, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Groby Road, Leicester, LE3 9QP, UK;2. School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK;3. Institute of Health Sciences Education, Queen Mary University of London, Barts Health NHS Trust, London, UK;4. UCLPartners, AHSN, London, UK;5. Clinical Effectiveness Unit, Royal College of Physicians of London, London, UK;2. Department of Orthopaedic Surgery, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA;3. Department of Medicine and the Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC 27599-7280, USA;4. Department of Biochemistry, Rush University Medical Center, 1653 W, Congress Parkway, Chicago, IL 60612, USA;6. Department of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA;1. Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL, USA;2. Institute of Applied Physics, Russian Academy of Sciences, Nizhny Novgorod, Russia;1. Medical Engineering Division, School of Engineering and Materials Science, Queen Mary, University of London, London, UK;2. Faculty of Health Sciences, University of Southampton, UK |
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| Abstract: | Chondrocytes are responsible for maintaining the cartilage that helps joints bear load and move smoothly. These cells typically respond to physiological compression with pathways consistent with matrix synthesis, and chondrocyte mechanotransduction is essential for homeostasis. In osteoarthritis (OA), chondrocyte mechanotransduction appears to be dysregulated, yet the mechanisms remain poorly understood. The objective of this study is to document the phosphoproteomic responses of primary osteoarthritic chondrocytes to physiological sinusoidal compression. We show that OA chondrocytes respond to physiological compression by first activating proteins consistent with cytoskeletal remodeling and decreased transcription, and then later activating proteins for transcription. These results show that several microtubule-related proteins respond to compression. Our results demonstrate that compression is a relevant physiological stimulus for osteoarthritic chondrocytes. Future analyses may build on these results to find differences in compression-induced phosphoproteins between normal and OA cells that lead to druggable targets to restore homeostasis to diseased joints. |
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| Keywords: | Chondrocyte biology Cartilage biomechanics Mechanobiology Mechanotransduction Cartilage repair Osteoarthritis |
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