Article: Delco, ML; Bonnevie, ED; Bonassar, LJ; Fortier, LA; “Mitochondrial Dysfunction is an Acute Response of Articular Chondrocytes to Mechanical Injury”, Journal of Orthopaedic Research, 36 (2): 739-750
Abstract: Mitochondrial (MT) dysfunction is known to occur in chondrocytes isolated from end-stage osteoarthritis (OA) patients, but the role of MT dysfunction in the initiation and early pathogenesis of post-traumatic OA (PTOA) remains unclear. The objective of this study was to investigate chondrocyte MT function immediately following mechanical injury in cartilage, and to determine if the response to injury differed between a weight bearing region (medial femoral condyle; MFC) and a non-weight bearing region (distal patellofemoral groove; PFG) of the same joint. Cartilage was harvested from the MFC and PFG of 10 neonatal bovids, and subjected to injurious compression at varying magnitudes (5-17MPa, 5-34GPa/s) using a rapid single-impact model. Chondrocyte MT respiratory function, MT membrane polarity, chondrocyte viability, and cell membrane damage were assessed in situ. Cartilage impact resulted in MT depolarization and impaired MT respiratory function within 2h of injury. Cartilage from a non-weight bearing region of the joint (PFG) was more sensitive to impact-induced MT dysfunction and chondrocyte death than cartilage from a weight-bearing surface (MFC). Our findings suggest that MT dysfunction is an acute response of chondrocytes to cartilage injury, and that MT may play a key mechanobiological role in the initiation and early pathogenesis of PTOA. Clinical significance: Direct therapeutic targeting of MT function in the early post-injury time frame may provide a strategy to block perpetuation of tissue damage and prevent the development of PTOA. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:739-750, 2018.
Funding Acknowledgement: Weill Cornell Medical College [5 UL1 TR000457-09]; National Institutes of Health [5T32OD011000-20]; Harry M. Zweig Memorial Fund for Equine Research; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1K08AR068470]
Funding Text: Grant sponsor: Weill Cornell Medical College; Grant number: 5 UL1 TR000457-09; Grant sponsor: National Institutes of Health; Grant number: 5T32OD011000-20; Grant sponsor: Harry M. Zweig Memorial Fund for Equine Research; Grant sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases; Grant number: 1K08AR068470.