Data & Analysis Code

AUTHORS:
Lena R. Bartell, Lisa A. Fortier, Lawrence J. Bonassar, Hazel
H. Szeto, Itai Cohen, and Michelle L. Delco.

ABSTRACT:
Post-traumatic osteoarthritis (PTOA) involves the mechanical
and biological deterioration of articular cartilage that occurs
following joint injury. PTOA is a growing problem in healthcare due to
the lack of effective therapies combined with an aging population with
high activity levels. Recently, acute mitochondrial dysfunction and
altered cellular respiration have been associated with cartilage
degeneration after injury. This finding is particularly important
because recently-developed mitoprotective drugs, including SS-peptides,
can preserve mitochondrial structure and function after acute injury in
other tissues. It is not known, however, if cartilage injury induces
peracute structural changes in mitochondria, to what degree
mitochondrial dysfunction in cartilage depends on the mechanics of
injury, or the time frame over which such dysfunction develops.
Similarly, it is unknown if SS peptide treatment can preserve
mitochondrial structure and function after cartilage injury. Here, we
combined fast-camera elastography, longitudinal fluorescence assays, and
computer vision techniques to track the fates of thousands of
individual cells. Our results show that impact induces
mechanically-dependent mitochondrial depolarization within a few minutes
after injury. Using electron microscopy, we further showed that impact
induces rapid structural changes in mitochondria that are related to
reduced mitochondrial function, namely fission and loss of cristae
structure. Remarkably, we find that SS-peptide treatment prior to impact
protects mitochondrial structure and preserves mitochondrial function
at levels comparable to that of unimpacted control samples. Overall,
this study reveals the vital role of mitochondria in mediating
cartilage’s peracute response to traumatic injury and demonstrates
mitoprotection as a promising therapeutic target for injury-induced
cartilage damage.