Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis. KEY MESSAGES: miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis.

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).

Closure with running subcuticular suture is cheaper and appears to have a clinical advantage when compared with metallic staples skin closure in primary THA surgery. However, additional operating time may be incurred.

Level II, prospective comparative study.

Background:With conflicting results in the literature, it remains unclear whether a higher field strength automatically increases the sensitivity and specificity of magnetic resonance imaging (MRI) for detecting pathological lesions in the knee. Therefore, we performed a systematic review and meta-analysis of studies comparing the diagnostic accuracy of 1.5- and 3.0-T MRI for lesions within the knee.Methods:Sixteen studies were included in the meta-analysis of the diagnostic accuracy of MRI for lesions of the knee joint, and areas under the curve (AUC) derived from the summary receiver operating characteristic curve analysis were determined for comparison of the diagnostic accuracy with differing magnetic field strength as well as for lesions in different tissues of the knee. Separate meta-analyses were performed for the diagnosis of lesions within articular cartilage, ligaments, and meniscus.Results:For lesions within the articular cartilage, the AUC for 1.5-T MRI differed significantly from that for 3.0-T MRI (Z = 3.4, P < .05). However, for lesions within the ligaments and meniscus, the AUC values for 1.5-T MRI did not differ significantly from those for 3.0-T MRI (Z = 0.32, P > .05, and Z = 0.33, P > .05, respectively).Conclusion:Our results indicate that both 1.5-T and 3.0-T MRI offer high diagnostic accuracy and clinical relevance for knee injuries involving the meniscus or a ligament. However, the present meta-analysis indicates that 3.0-T MRI does offer greater diagnostic accuracy than 1.5-T MRI for articular cartilage lesions.

Objective Growing evidence indicates that microRNAs (miRNA) play a critical role in the pathogenesis of OA, and overexpressing or silencing miRNA expression in OA models can contribute to the development of miRNA-based therapeutics. The objective of this study was to determine whether intra-articular injection of miRNA can inhibit OA progression. Methods The miRNA expression profile was determined in OA cartilage tissues and controls. Functional analysis of the miRNAs on extracellular matrix degradation was performed after miRNA mimic or inhibitor transfection. Luciferase reporter assays and western blotting were employed to determine miRNA targets. To investigate the functional mechanism of miR-21-5p in OA development, miR-21-5pfl/flCol2a1-CreER and wild-type mice were subject to surgical destabilization of the medial meniscus. Therapeutically, wild-type mice undergoing surgical destabilization of the medial meniscus were treated with intra-articular injection of agomir- and antagomir-21-5p. Results We found that expression of miR-21-5p was significantly up-regulated in OA cartilage tissues. The articular cartilage degradation of miR-21-5p conditional knockout mice was significantly alleviated compared with that of wild-type mice in spontaneous and destabilization of the medial meniscus models. Through gain-of-function and loss-of-function studies, miR-21-5p was shown to significantly affect matrix synthesis genes expression, and chondrocyte proliferation and apoptosis. Further, fibroblast growth factor 18 (FGF18) was identified as a target of miR-21-5p. Intra-articular injection of antagomir-21-5p significantly attenuated the severity of experimental OA. Clinically, FGF18 expression level was correlated with miR-21-5p expression and a modified Mankin scale. Conclusion Our findings reveal a miRNA functional pathway important for OA development, highlighting miRNA-21-5p silencing as an attractive therapeutic regimen in future clinical trials involving patients with OA.

No abstract

Most patients with ONFH induced by steroids complained of pain within 3 years of commencing steroid therapy. Pain was associated with lesion size, collapse and BME. Atypical location of pain, failure to perform a physical examination and MRI findings were the main causes of misdiagnoses.