MicroRNA-17-5p contributes to osteoarthritis progression by binding p62/SQSTM1.

Autophagy has been reported to be widely involved in the pathogenesis of osteoarthritis (OA). Increasing evidence suggested the important role of microRNAs (miRs) in the progression of OA. However, the functional role of miR-17-5p in OA development has remained to be fully elucidated. First, a mouse model of OA was established and the relative level of miR-17-5p was determined using PCR. Safranin O-fast green staining was applied to determine cartilage degeneration. TargetScan software and a dual luciferase reporter assay were applied to determine potential target genes of miR-17-5P. Autophagy measurement was performed using green fluorescent protein-microtubule-associated protein 1 light chain 3 (LC3) dot analysis. The results demonstrated that the relative expression of miR-17-5p was significantly decreased in OA model mice. In addition, the level of miR-17-5p was decreased in SW1353 human chondrosarcoma cells treated with interleukin-1ß. Furthermore, autophagy was found to be suppressed in the knee joints of experimental OA model mice. The dual luciferase reporter assay confirmed that p62/sequestosome 1 was a target gene of miR-17-5p. Of note, miR-17-5p inhibitor-induced reduction of LC3 dots was markedly reversed by knockdown of p62 in SW1353 cells. In conclusion, decreased miR-17-5p expression in chondrocytes induced autophagy mainly through suppressing the expression of p62, thereby contributing to OA progression.

[Anatomical study on the reconstruction of the metacarpal bone with autogenous iliac crest grafting].

OBJECTIVE: To explore the similarity between the iliac crest and the metacarpal bone, so as to provide an anatomical basis for the reconstruction of the metacarpal bone of the hand with the iliac crest grafting. METHODS: There are 16 upper limb specimens and 10 pelvic specimens. The morphological features of the second, third, fourth and 5th metacarpal bones and iliac crest were observed. The following indexes were measured: arc height and length of metacarpal head articular surface, volar-dorsal metacarpal diameter, ulnoradial diamater, arc height and length of iliac crest, and inner and outer diameter. The obtained data were statistically analyzed to compare the morphological, structural features, arc length and diameter length of each metacarpal bone and iliac crest. RESULTS: The arc length of the second metacarpal head, volar-dorsal metacarpal diameter, arc height, and the ulnoradial diameter are 22.040(21.425, 23.085) mm, (14.034±0.465) mm, 4.185 (4.113, 4.598) mm, and (12.227±0.414) mm respectively. The arc length of the third metacarpal head, volar-dorsal metacarpal diameter, arc height, and the ulnoradial diameter are 23.430(22.743, 24.153)mm, (14.316±0.430) mm, 4.235(4.170, 4.670) mm, and (12.382±0.425) mm respectively. The arc length of the fourth metacarpal head, volar-dorsal metacarpal diameter, arc height, and the ulnoradial diameter are 21.960 (21.245, 22.285) mm, (12.382±0.288) mm, 4.125 (4.030, 4.305) mm, and (11.991±0.362) mm respectively. The arc length of the fifth metacarpal head, volar-dorsal metacarpal diameter, arc height, and the ulnoradial diameter are 20.030 (19.668, 20.148) mm, (11.807±0.358) mm, 4.015(3.880, 4.205) mm, and (11.659±0.399) mm respectively. The inner and outer diameter of the iliac crest is 14.350 (13.660, 14.739) mm, and the arc length and height are (22.930±0.701) mm and (4.520±0.184) mm respectively. The difference between the volar-dorsal metacarpal diameter of the second metacarpal head and the inner and outer diameter of the iliac crest has no significant; while the volar-dorsal metacarpal diameter of the third, fourth and fifth metacarpal heads are apparently longer and shorter than the inner and outer diameter of the iliac crest, respectively. The differences are statistically significant. The differences between arc length of the iliac crest and arc length of the second, fourth and fifth metacarpl head are statistically significant. However, the difference of arc length between the third metacarpal head and the ilium, as well as the difference of arc height between the second and third metacarpal heads and the iliac crest have no statistical significances, while the arc height of the fourth and fifth metacarpal heads are obviously smaller than that of the iliac crest. CONCLUSIONS: Autologous iliac crest is similar with metacarpal bone in anatomy, which might be a suitable donor for metacarpal bone transplantation.

Leptin modulates the expression of catabolic genes in rat nucleus pulposus cells through the mitogen-activated protein kinase and Janus kinase 2/signal transducer and activator of transcription 3 pathways.

Obesity has been demonstrated to be involved in the progress of intervertebral disc degeneration (IDD). However, the associated mechanisms remain to be elucidated. The purpose the present study was to examine the effect of leptin on the expression of degeneration-associated genes in rat nucleus pulposus (NP) cells, and determine the possible mechanism. Normal NP cells, obtained from Sprague Dawley rats, were identified using immunocytochemistry for the expression of collagen II and CA125, and treated with leptin and/or interleukin (IL)-ß. Subsequently, the mRNA expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, aggrecan and COL2A1 were detected by reverse transcription-quantitative polymerase chain reaction (RT-q-PCR). Alcian staining and immunocytochemistry were used to examine the expression levels of proteoglycan and collagen II. The pathway activation was investigated using western blotting, and inhibitors of the pathways were used to reveal the effect of these pathways on the NP cells. The results of the RT-qPCR demonstrated that leptin alone upregulated the mRNA expression levels of MMP-1, MMP-13, ADAMTS-4, ADAMTS-5 and COL2A1. Synergy of leptin and IL-ß was found in the increased expression levels of MMP-1, MMP-3 and ADAMTS-5. The leptin-treated NP cells exhibited decreased expression of collagen II. The mitrogen-activated protein kinase (MAPK) pathway (c-Jun-N-terminal kinase, phosphorylated extracellular signal-regulated kinase and p38), phosphatidylinositol 3-kinase (PI3K)/Akt pathway and Janus kinase (JAK)2/signal transducer and activator of transcription 3 pathway were all activated by leptin, however, inhibitors of all the pathways, with the exception of the PI3K/Akt pathway, reversed the expression levels of MMP-1 and MMP-13. These results suggested that leptin promoted catabolic metabolism in the rat NP cells via the MAPK and JAK2/STAT3 pathways, which may be the mechanism mediating the association between obesity and IDD.

[Case control study on therapeutic effects of dynamic external fixtor combined with limited internal fixation and cross K-wires fixation for the treatment of Pilon fractures of the proximal interphalangeal joint].

OBJECTIVE: To compare the clinical effects and safety of dynamic external fixtor combined with limited internal fixation and cross K-wires fixation for the treatment of close Pilon fractures of the proximal interphalangeal joint. METHODS: From June 2012 to June 2014, totally 41 patients (45 fingers) with close interphalangeal joint Pilon fracture were treated by dynamic external fixtor combined with limited internal fixation or cross K-wires fixation, and all the patients were followed up. In the dynamic external fixtor combined with limited internal fixation group (group A), there were 21 patients with 22 fingers, including 12 males and 9 females, with an average of (30.6±5.6) years old. In the cross K-wires fixation group (group B), there were 20 patients with 23 fingers, including 11 males and 9 females, with an average of (30.1±5.3) years old. Regular re-examination of X-ray was performed to evaluate the active range of joint motion, fracture healing time, infection rate and postoperative joint motion pain. RESULTS: According to the evaluation criteria of upper extremity function issued by the Hand Surgery Society of Chinese Medical Association, the excellent and good cases of group A was up to 19 and 13 for group B. The evaluation results has significant differences (Z=2.558, P=0.011). The excellent and good rate of group A was obviously higher than that of group B. The average bone union time of group A was (7.9±2.1) weeks, and (8.1±2.3) weeks for group B. There was no significant difference on the mean healing time (t=-0.304, P=0.762). The infection fingers of group A was 5, and 1 for group B. The difference between the results was statistically significant (χ2=3.287, P<0.05). The infection rate of group A was higher than that of group B. The postoperative joint motion pain was evaluated by VAS score, the mean score was 0.18±0.50 in group A, and 0.65±0.88 in group B. The difference between the results was statistically significant (t=-2.207, P<0.05). The postoperative joint motion pain was lower than that of group B. CONCLUSION: Dynamic external fixtor combined with limited internal fixation is a reliable and effective method to treat Pilon fractures of the proximal interphalangeal joint. It allows early postoperative functional rehabilitation and restores the joint function.

Toll-like receptor 4 is required for the cytotoxicity of cytokine-induced killer cells.

Cytokine-induced killer (CIK) cells are heterogeneous effector T cells with diverse T-cell receptor specificities with non-major histocompatibility complex-restricted cytolytic activities against tumor cells and are considered a promising therapeutic approach against hematologic malignancy. Recently, it has been reported that IL-15-activated CIK cells are superior to cells generated according to the standard protocol; however, the underlying mechanism remains to be elucidated. In the present study, we found that in IL-15-stimulated CIK cells, Toll-like receptor 4 (TLR4) expression was upregulated. Upon knockdown of TLR4, the cytolytic activity was considerably compromised. Re-expression of TLR4 in CIK cells restored their function, confirming the essential role of TLR4 in CIK cell cytotoxicity. Collectively, our study demonstrated that TLR4 was essential for the cytotoxicity of CIK cells against tumor cells, which might provide a novel approach to promote the therapeutic efficacy of CIK cells against hematologic malignancy.