The T2 value changes reflected histologic tendon healing. While T2 and Bonar grade were lower at all time points in tendons treated with PRP, there was no significant difference between the treatment and control tendons.
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 ...
Partial thickness articular cartilage injuries (PTCIs) were not previously thought to heal spontaneously. Immature rats have the capacity for spontaneous repair of PTCIs, although it is a long-term process. Our aim has been to examine the spontaneous repair response mechanism in immature rats. Single linear PTCIs were created in 3-week-old and 12-week-old rats in the direction of joint motion. On day 1 and at 1, 2, and 4 weeks after PTCI, evaluations of histological changes and immunohistology at the injury site and in the surrounding cartilage were performed. Anti-CD105 and anti-CD166 antibodies (as stem cell markers to identify mesenchymal stem cells in reparative cartilage tissue) were used for immunohistological evaluations. To determine whether endogenous repair ability existed in articular cartilage, an ex vivo experiment was also carried out. Femoral condyles with PTCIs were incubated in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum for 1 day and for 1 and 2 weeks. Histological changes were subsequently examined. Immature cartilage showed a higher repair response than did mature cartilage, and the response occurred immediately after PTCI. In immature rats, CD105- and CD166-positive cells were found in the superficial and transitional zones of the articular cartilage. Few CD166-positive cells were identified in mature articular cartilage. No significant in vivo differences in the spontaneous repair responses to PTCIs were observed between mature and immature groups. Thus, the repair response to PTCIs seems to be associated not only with CD105- and CD166-positive cells, but also with other perichondral factors.
BackgroundThe aims of this study were to reveal the characteristics of the meniscal shape at each knee osteoarthritis (OA) severity level and to predict trends or patterns of the meniscal shape change as associated with knee OA progression.MethodsFifty-one patients diagnosed with knee OA based on X-ray and magnetic resonance (MR) images were evaluated. They were divided into three groups based on the Kellgren–Lawrence (KL) grade: normal group (KL grade of 0 or 1), mild group (KL grade of 2 or 3), and severe group (KL grade of 4). We measured the patients’ meniscal size and meniscal extrusion using MR images. In addition, semiquantitative measurement was performed using MR images to determine the arthritic status of the corresponding compartment using a whole-organ magnetic resonance imaging score (WORMS).ResultsThe longitudinal diameter and posterior wedge angle of the medial meniscus were significantly larger, and the posterior wedge width of the medial meniscus was significantly smaller in the severe group than in the normal group. The WORMS scores for cartilage and osteophytes in the medial region were significantly different among the groups. The WORMS score of each region was strongly correlated with the longitudinal diameter. The WORMS scores of the lateral region were lower than those of the medial region.ConclusionOur observation of the shape change of the medial meniscus in the posterior region was roughly consistent with that in many previous studies of meniscal degeneration. On the other hand, we saw that the most relevant relation between the progression of the knee OA and the deformation of the meniscus was in the longitudinal direction.
T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation.
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