Objective To quantify functional age-related changes in the cartilage antioxidant network to discover novel mediators of cartilage oxidative stress and osteoarthritis (OA) pathophysiology. Methods We evaluated knee OA histopathology in 10, 20, and 30-month old male F344BN rats and analyzed cartilage oxidation by the ratio of reduced:oxidized glutathione. Antioxidant gene expression and protein abundance were analyzed by qRT-PCR and selected reaction-monitoring mass spectrometry, respectively. Superoxide dismutase 2 (SOD2) activity and acetylation were analyzed by colorimetric enzyme assays and Western blotting, respectively. We examined human OA cartilage to evaluate the clinical relevance of SOD2 acetylation, and we tested age-related changes in the mitochondrial deacetylase, sirtuin 3 (SIRT3), in rats and mice. Results Cartilage oxidation and OA severity increased with age and were associated with an increase in SOD2 expression and protein abundance. However, SOD2 specific activity decreased with age due to elevated post-translational lysine acetylation. Consistent with these findings, SIRT3 decreased substantially with age, and treatment with SIRT3 increased SOD2 activity in an age-dependent manner. SOD2 was also acetylated in human OA cartilage, and activity was increased with SIRT3 treatment. Moreover, in C57BL6 mice, cartilage SIRT3 expression decreased with age and whole-body deletion of SIRT3 accelerated the development of knee OA. Conclusion Our results show that SIRT3 mediates age-related changes in cartilage redox regulation and protects against early-stage OA. These findings suggest that mitochondrial acetylation promotes OA and that restoration of SIRT3 in aging cartilage may improve cartilage resistance to oxidative stress by rescuing acetylation-dependent inhibition of SOD2 activity.

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Background Complications are frequent with osteoarticular allografts, and their long-term survivorship in the distal femur is unclear. Thus, the benefits of osteoarticular allografting remain controversial. Questions/purposes We therefore determined the frequency of complications in osteoarticular allografts of the distal femur relative to their potential long-term survival. Methods We retrospectively reviewed 26 patients who had osteoarticular allograft reconstruction of the distal femur after resection of a malignant or aggressive benign tumor of bone. The minimum followup was 15 months (average, 156 months; range, 15-283 months) for all patients and 98 months (average, 191 months; range, 98-283 months) for the surviving patients.Results At last followup, 16 of the 26 original allografts were still in place. The overall 5-year and 10-year allograft survival rates were 69% and 63%, respectively. The 5-year and 10-year survival rates of the joint surface were 79% and 65%, respectively. Eleven patients retained their original osteoarticular allograft without a resurfacing procedure, and nine had been converted to allograft-prosthetic composites. Five patients were converted to megaprostheses and one had an amputation for local recurrence. At last followup, 25 of 26 patients retained a functional limb.

Acarbose, through its unique mechanism of action, appears to be a safe and effective adjunctive agent to diet/exercise therapy or sulfonylurea therapy for treatment of non-insulin-dependent diabetes mellitus.

This information can assist the fellowship directors and related professional societies in tailoring their educational programs and the interested orthopaedic resident to make a more informed career choice.