A better understanding of molecular events following cartilage injury is required to develop treatments that prevent or delay the onset of trauma-induced osteoarthritis. In this study, alterations to SIRT1 activity in bovine articular cartilage explants were evaluated in the 24 h following a mechanical overload, and the effect of pharmacological SIRT1 activator SRT1720 on acute chondrocyte injury was assessed. SIRT1 enzymatic activity decreased as early as 5 min following the mechanical overload, and remained suppressed for at least 24 h. The chondrocyte injury response, including apoptosis, oxidative stress, secretion of inflammatory mediators, and alterations in cartilage matrix expression, was prevented with pharmacological activation of SIRT1 in a dose-dependent manner. Overall, the results implicate SIRT1 deactivation as a key molecular event in chondrocyte injury following a mechanical impact overload. As decreased SIRT1 signaling is associated with advanced age, these findings suggest that downregulated SIRT1 activity may be common to both age-related and injury-induced osteoarthritis.

Post-Traumatic Osteoarthritis (PTOA) is a prevalent, degenerative, and painful progressive joint disease that typically arises after significant joint trauma, affecting over 6 million Americans. Impact-induced cartilage trauma results in a chondrocyte injury response that culminates in PTOA. Understanding the molecular events associated with chondrocyte injury is necessary to develop therapies to prevent PTOA or slow its progression. To facilitate this, an ex vivo cartilage impact model that was sublethal for 24 h was developed. Osteochondral explants were harvested from bovine metacarpophalangeal joints, and a drop tower was used to deliver impact loads to the explants. To ensure that the stress and impact were applied relatively uniformly to the articular cartilage, explants were positioned with the bone surface facing upward, and the bone was impacted from above. Different loads were applied to the explants from carriage heights of 4.0 cm, 4.5 cm, and 5.0 cm, resulting in average peak stresses of 10.87 ± 1.84 MPa, 11.69 ± 0.67 MPa, and 12.98 ± 0.75 MPa, respectively. The study analyzed the role of subchondral bone presence in cartilage during post-impact culture and the effect of using either a fitted or loose holder during impact, assessing cell viability and apoptosis. Articular cartilage impacted from 4.5 cm, combined with a fitted holder and immediate bone removal, provided the optimal model to induce cartilage injury with minimal cell death at 24 h post-impact.

Post-Traumatic Osteoarthritis (PTOA) is a prevalent, degenerative, and painful progressive joint disease that typically arises after significant joint trauma, affecting over 6 million Americans. Impact-induced cartilage trauma results in a chondrocyte injury response that culminates in PTOA. Understanding the molecular events associated with chondrocyte injury is necessary to develop therapies to prevent PTOA or slow its progression. To facilitate this, an ex vivo cartilage impact model that was sublethal for 24 h was developed. Osteochondral explants were harvested from bovine metacarpophalangeal joints, and a drop tower was used to deliver impact loads to the explants. To ensure that the stress and impact were applied relatively uniformly to the articular cartilage, explants were positioned with the bone surface facing upward, and the bone was impacted from above. Different loads were applied to the explants from carriage heights of 4.0 cm, 4.5 cm, and 5.0 cm, resulting in average peak stresses of 10.87 ± 1.84 MPa, 11.69 ± 0.67 MPa, and 12.98 ± 0.75 MPa, respectively. The study analyzed the role of subchondral bone presence in cartilage during post-impact culture and the effect of using either a fitted or loose holder during impact, assessing cell viability and apoptosis. Articular cartilage impacted from 4.5 cm, combined with a fitted holder and immediate bone removal, provided the optimal model to induce cartilage injury with minimal cell death at 24 h post-impact.