Delco Michelle L, Bonnevie Edward D, Bonassar Lawrence J, Fortier Lisa A
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York.
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.
J Orthop Res. 2018 Feb;36(2):739-750. doi: 10.1002/jor.23651. Epub 2017 Jul 31.
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 (5-17 MPa, 5-34 GPa/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 2 h 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.
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. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:739-750, 2018.
已知从终末期骨关节炎（OA）患者分离出的软骨细胞会出现线粒体（MT）功能障碍，但MT功能障碍在创伤后骨关节炎（PTOA）的起始和早期发病机制中的作用仍不清楚。本研究的目的是调查软骨受到机械损伤后立即出现的软骨细胞MT功能，并确定同一关节的负重区域（股骨内侧髁；MFC）和非负重区域（髌股远侧沟；PFG）对损伤的反应是否不同。从10只新生牛的MFC和PFG采集软骨，并使用快速单次冲击模型以不同幅度（5 - 17MPa，5 - 34GPa/s）进行损伤性压缩。原位评估软骨细胞MT呼吸功能、MT膜极性、软骨细胞活力和细胞膜损伤情况。软骨冲击导致损伤后2小时内MT去极化和MT呼吸功能受损。与来自负重表面（MFC）的软骨相比，关节非负重区域（PFG）的软骨对冲击诱导的MT功能障碍和软骨细胞死亡更敏感。我们的研究结果表明，MT功能障碍是软骨细胞对软骨损伤的急性反应，并且MT可能在PTOA的起始和早期发病机制中起关键的力学生物学作用。
在损伤后的早期时间框架内直接针对MT功能进行治疗可能提供一种策略，以阻止组织损伤的持续并预防PTOA的发展。©2017骨科研究协会。由Wiley Periodicals, Inc.出版。《矫形外科研究杂志》36:739 - 750, 2018。
