Downregulation of miR-221-3p contributes to IL-1ß-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway.

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-1ß 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-1ß, 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-1ß-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-1ß-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-1ß-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.

[Effect of admission blood urea and creatinine levels on mortality in elderly patients with hip fracture].

OBJECTIVE: To observe the effect of admission blood urea and creatinine levels on mortality in elderly patients with hip fracture. METHODS: Form January 2013 to December 2014, 767 elder patients with hip fracture were treated in our hospital including 253 males and 514 females, aged from 65 to 96 years old with an average of(75.67±6.81) years old. According blood urea and creatinine levels, the 767 hip fracture patients were divided into four groups as follow: group A(blood urea>=5 mmol/L, creatinine>=70 µmol/L); group B (blood urea>=5 mmol/L, creatinine<70 µmol/L); group C (blood urea<5 mmol/L, creatinine>=70 µmol/L); group D(blood urea<5 mmol/L, creatinine<70 µmol/L). In group A, there were 211 patients including 70 males and 141 females, aged from 65 to 95 years old with an average of(80.24±6.51) years old; in group B, there were 355 patients including 125 males and 230 females, aged from 65 to 93 years old with an average of(78.46±7.09) years old; in group C, there were 36 patients including 11 males and 25 females, aged from 65 to 95 years old with an average of (77.83±6.78) years old; in group D, there were 165 patients including 47 males and 118 females, aged from 65 to 96 years old with an average of (76.71±8.35) years old. The survivals and dead patients in four groups were collected and in-hospital mortality rate, 3-month, 12-month and 18-month mortality rate of patients were calculated. COX regression analysis was performed on these data, and clinical significance of serum urea and creatinine at admission in the elderly patients was researched. RESULTS: All 767 hip fracture patients were followed up from 18 to 24 months with an average of (21.33±1.25) months, 159 patients were died in follow up period. The in-hospital mortality rate in 3-month, 12-month and 18-month mortality rate of the patients with high blood urea and high blood creatinine (urea>=5 mmol/L, creatinine>=70 µmol/L) were 2.37%, 9.95%, 16.11% and 26.07%, and were higher than other three groups respectively. COX regression analysis revealed that the independent predictors effecting the mortality rate included age [P=0.000, OR=1.375, 95%CI(1.155, 1.637)], blood urea at admission [P=0.000, OR=1.375, 95%CI(1.155, 1.637)], and blood creatinine at admission[P=0.037, OR=1.213, 95%CI(1.121, 1.484)]. CONCLUSIONS: Elderly hip fracture patients with high serum urea and high serum creatinine at admission indicate higher fatality rate. Age, serum urea and serum creatinine at admission were independent predictors of fatality rate of elderly hip fracture patients.