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Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function
Author(s) -
Coleman Mitchell C.,
Ramakrishnan Prem S.,
Brouillette Marc J.,
Martin James A.
Publication year - 2016
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39460
Subject(s) - chondrocyte , oxidative stress , reactive oxygen species , cartilage , chemistry , osteoarthritis , mitochondrion , glutathione , andrology , medicine , anatomy , endocrinology , biochemistry , pathology , alternative medicine , enzyme
Objective To determine whether repeatedly overloading healthy cartilage disrupts mitochondrial function in a manner similar to that associated with osteoarthritis (OA) pathogenesis. Methods We exposed normal articular cartilage on bovine osteochondral explants to 1 day or 7 consecutive days of cyclic axial compression (0.25 MPa or 1.0 MPa at 0.5 Hz for 3 hours) and evaluated the effects on chondrocyte viability, ATP concentration, reactive oxygen species (ROS) production, indicators of oxidative stress, respiration, and mitochondrial membrane potential. Results Neither 0.25 MPa nor 1.0 MPa of cyclic compression caused extensive chondrocyte death, macroscopic tissue damage, or overt changes in stress–strain behavior. After 1 day of loading, differences in respiratory activities between the 0.25 MPa and 1.0 MPa groups were minimal; however, after 7 days of loading, respiratory activity and ATP levels were suppressed in the 1.0 MPa group relative to the 0.25 MPa group, an effect prevented by pretreatment with 10 m M N ‐acetylcysteine. These changes were accompanied by increased proton leakage and decreased mitochondrial membrane potential, as well as by increased ROS formation, as indicated by dihydroethidium staining and glutathione oxidation. Conclusion Repeated overloading leads to chondrocyte oxidant‐dependent mitochondrial dysfunction. This mitochondrial dysfunction may contribute to destabilization of cartilage during various stages of OA in distinct ways by disrupting chondrocyte anabolic responses to mechanical stimuli.