Metabolic responses induced by compression of chondrocytes in variable-stiffness microenvironments |
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| Affiliation: | 1. Department of Mechanical & Industrial Engineering, Montana State University, United States;2. Department of Cell Biology & Neurosciences, Montana State University, United States;3. Department of Orthopaedics & Sports Medicine, University of Washington, United States;1. Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands;2. Department of Orthopedic Surgery, State University of New York, Upstate Medical University, Syracuse, NY, USA;3. University of Twente, Laboratory for Biomechanical Engineering, Faculty of Engineering Technology, Enschede, The Netherlands;1. Department of Medicine (DIMED), Geriatrics Division, University of Padova, Italy;2. Department of Geriatrics, Azienda Sanitaria dell''Alto Adige, Bolzano, Italy;3. Emergency Department, Azienda Sanitaria dell''Alto Adige, Bolzano, Italy;4. National Research Council, Institute of Neuroscience, Aging Branch, Padova, Italy;1. Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan;2. Division of Dental Informatics, Osaka University Dental Hospital, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan;1. Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA;2. PERCRO Laboratory, TeCIP Institute, Scuola Superiore Sant’Anna, via Alamanni 13b, 56010 Ghezzano, San Giuliano Terme, Pisa, Italy;3. Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA;1. Department of Mechanical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA;2. MSU Center for Orthopedic Research, College of Osteopathic Medicine, Michigan State University, Lansing, MI, USA;3. Department of Osteopathic Surgical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA;4. School of Mechanical Engineering, Yonsei University, Seoul, Republic of Korea |
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| Abstract: | Cells sense and respond to mechanical loads in a process called mechanotransduction. These processes are disrupted in the chondrocytes of cartilage during joint disease. A key driver of cellular mechanotransduction is the stiffness of the surrounding matrix. Many cells are surrounded by extracellular matrix that allows for tissue mechanical function. Although prior studies demonstrate that extracellular stiffness is important in cell differentiation, morphology and phenotype, it remains largely unknown how a cell’s biological response to cyclical loading varies with changes in surrounding substrate stiffness. Understanding these processes is important for understanding cells that are cyclically loaded during daily in vivo activities (e.g. chondrocytes and walking). This study uses high-performance liquid chromatography – mass spectrometry to identify metabolomic changes in primary chondrocytes under cyclical compression for 0–30 minutes in low- and high-stiffness environments. Metabolomic analysis reveals metabolites and pathways that are sensitive to substrate stiffness, duration of cyclical compression, and a combination of both suggesting changes in extracellular stiffness in vivo alter mechanosensitive signaling. Our results further suggest that cyclical loading minimizes matrix deterioration and increases matrix production in chondrocytes. This study shows the importance of modeling in vivo stiffness with in vitro models to understand cellular mechanotransduction. |
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| Keywords: | Chondrocyte mechanotransduction Cartilage repair Substrate stiffness Osteoarthritis |
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