This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR).Objectives
Methods
Femoral lengthening has been associated with narrowing of the joint space at the hip. We have studied the joint space before lengthening in 20 patients with a short femur due to a femoral-shaft fracture (15) or distal femoral epiphyseal injury (5). Their mean age at injury was 16 years (3 to 27) and the mean shortening was 5.4 cm (1.1 to 14). We found that the hip joint space of the shortened femur was significantly narrower (p <
0.001) than that on the normal side, with a mean narrowing ratio of 15.5% (−5 to +43). The narrowing ratio was directly related to the period spent non-weight-bearing (p <
0.001), but not to the amount of femoral shortening. We have shown that the joint space of the hip in patients with post-traumatic femoral shortening was narrowed even before femoral lengthening had been started.
