Angiogenic activity of subchondral bone was elevated in the early to progressive stage of OA and vascular invasion into the osteochondral junction followed.
The findings of this study suggest that ultrasound examination may be suitable for screening for meniscal tears. The fact that almost 10% of the lateral menisci could not be evaluated because of poor images appears to be a weakness of ultrasound.
This study investigated the effect of MMP-13 gene knock down on cartilage degradation by injecting small interfering RNA (siRNA) into knee joints in a mouse model of osteoarthritis (OA). OA was induced in male C57BL/6 mice by destabilization of medial meniscus (DMM) surgery. Change of Mmp13 expression over time was determined by qPCR analysis from 3 days to 6 weeks after surgery. Mmp13 and control chemically modified siRNA were injected into the knee joint 1 week after surgery and expression levels were assessed in synovium by qPCR 48 h later. Cartilage degradation was histologically assessed 8 weeks after DMM surgery according to OARSI recommendations. Mmp13 expression levels were elevated 1 week after surgery and peaked at 77 fold at 2 weeks compared to expression at 3 days. A 55% decrease of Mmp13 levels in cartilage was observed 48 h after injection of Mmp13 siRNA (p ¼ 0.05). Significant reduction in the histological score at 8 weeks after surgery was observed in the Mmp13 siRNA-treated group compared to the control siRNA group (p < 0.001). Intra-articular injection of Mmp13 siRNA at the early phase of OA development resulted in effective knock down of Mmp13 expression and delay in cartilage degradation in vivo. Keywords: MMP-13; siRNA; in vivo; mouse; DMM In the pathogenesis of osteoarthritis (OA), matrix metalloproteinase (MMP)-13 play an important role in the early phase of cartilage degradation due to its preferential digestion of type II collagen. 1 Studies using MMP-13 knockout mice 2 or MMP inhibitors [3][4][5] have demonstrated prevention of cartilage degradation in animal OA models, which suggests MMP inhibition as a therapeutic modality for OA. While most studies focus on MMP-13 expression in OA cartilage, 6,7 synovial membrane is also considered as an important source of MMP-13 in OA. 1,8 RNA interference (RNAi) offers enormous potential as a therapeutic agent. Small interfering RNAs (siRNAs) have proven to be beneficial in knocking down protease effects in vitro, 9 but there are still difficulties in delivery in vivo. 10 To avoid siRNA degeneration in serum, recent studies suggest local injection as an alternative method of siRNA delivery to specific organs. [11][12][13] Chemically modified siRNAs that do not require techniques such as liposomes or electroporation when transfecting cells have been developed. These siRNAs can be applied to cells with low cellular toxicity and are therefore likely to be suitable for in vivo use. 9,11,12,14 In this study, we aimed to evaluate the effect of Mmp13 knockdown on cartilage degradation by directly injecting chemically modified siRNAs into knee joints of mice with surgically-induced OA. To our knowledge, this is the first study to report the effect of direct in vivo application of siRNA in an animal OA model. Our hypothesis was that direct injection of siRNA in the knee joint could effectively reduce development of OA in vivo.
MATERIALS AND METHODS
AnimalsMale C57BL/6 mice were purchased from Japan SLC (Hamamatsu, Japan). Animal experiments were ...
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