Mitoprotective therapy preserves chondrocyte viability and prevents cartilage degeneration in an ex vivo model of posttraumatic osteoarthritis

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Michelle L DelcoLisa A Fortier

Abstract

No disease-modifying osteoarthritis (OA) drugs are available to prevent posttraumatic osteoarthritis (PTOA). Mitochondria (MT) mediate the pathogenesis of many degenerative diseases, and recent evidence indicates that MT dysfunction is a peracute (within minutes to hours) response of cartilage to mechanical injury. The goal of this study was to investigate cardiolipin-targeted mitoprotection as a new strategy to prevent chondrocyte death and cartilage degeneration after injury. Cartilage was harvested from bovine knee joints and subjected to a single, rapid impact injury (24.0 ±1.4 MPa, 53.8 ± 5.3 GPa/s). Explants were then treated with a mitoprotective peptide, SS-31 (1µM), immediately post-impact, or at 1, 6, or 12 h after injury, and then cultured for up to 7 days. Chondrocyte viability and apoptosis were quantified in situ using confocal microscopy. Cell membrane damage (lactate dehydrogenase activity) and cartilage matrix degradation (glycosaminoglycan loss) were quantified in cartilage-conditioned media. SS-31 treatment at all time points after impact resulted in chondrocyte viability similar to that of un-injured controls. This effect was sustained for up to a week in culture. Further, SS-31 prevented impact-induced chon...Continue Reading

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Citations

Dec 17, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Lena R BartellMichelle L Delco
Feb 29, 2020·International Journal of Molecular Sciences·Jana Riegger, Rolf E Brenner
Feb 9, 2021·Frontiers in Bioengineering and Biotechnology·Marietta HerrmannSusanne Grässel
Feb 17, 2021·Signal Transduction and Targeted Therapy·Delin LiuJunjie Gao
May 8, 2018·Journal of Biomechanics·Edward D BonnevieLawrence J Bonassar
Mar 19, 2021·Bone Research·Yan HuJiacan Su
Apr 25, 2021·Current Rheumatology Reports·Piedad C Gomez-ContrerasMitchell C Coleman
Jun 25, 2021·Nature Reviews. Rheumatology·Michelle L Delco, Lawrence J Bonassar
Jul 6, 2021·Frontiers in Pharmacology·Yuchen HeHang Lin
Dec 5, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Steven AyalaLawrence J Bonassar
Dec 23, 2021·Nature Reviews. Rheumatology·Tom HodgkinsonFergal J O'Brien

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