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1.
Int Immunopharmacol ; 83: 106425, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32247266

RESUMO

Increasing evidence has demonstrated that the dysregulated expression of long noncoding RNAs (lncRNAs) has important roles in the progression of osteoarthritis (OA), but the function of the lncRNA SNHG15 remains unclear. In the present study, we observed that SNHG15 was downregulated in OA cartilage tissues and IL-1ß-induced chondrocytes. The lower expression of SNHG15 was negatively associated with the observed modified Mankin scale scores, extracellular matrix (ECM) degradation and chondrocyte apoptosis. Downregulated expression of SNHG15 increased chondrocyte viability and decreased chondrocyte apoptosis and ECM degradation in vitro and reduced damage to articular cartilage in vivo. Mechanistically, we demonstrated that SNHG15 overexpression promotes the expression of BCL2L13 by sponging miR-141-3p. The higher expression of miR-141-3p was negatively correlated with SNHG15 and BCL2L13 levels in OA cartilage tissues, and a positive correlation was also shown between SNHG15 and BCL2L13 levels. Furthermore, ectopic expression of miR-141-3p or knockdown of BCL2L13 expression could both reduce the effects of SNHG15 on chondrocyte proliferation, apoptosis and ECM degradation. Collectively, these findings reveal that SNHG15 inhibits OA progression by acting as an miR-141-3p sponge to promote BCL2L13 expression, suggesting that knockdown of SNHG15 expression in chondrocytes can be a potential therapeutic strategy to ameliorate OA progression.


Assuntos
Condrócitos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Apoptose/genética , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Proliferação de Células/genética , Progressão da Doença , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Interleucina-1beta/metabolismo , Masculino , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos , Ratos Sprague-Dawley
2.
Med Sci Monit ; 25: 3655-3661, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31097682

RESUMO

BACKGROUND This retrospective study compared the effects of total hip arthroplasty (THA) and traditional surgery using internal screw fixation for the treatment of avascular necrosis (AVN) of the femoral head. MATERIAL AND METHODS A total of 270 patients with bilateral ANFH were retrospectively analyzed. Among them, 176 underwent THA (THA group); and 94 underwent closed reduction screw fixation (traditional group).  RESULTS The mean operation time in the traditional surgery group (82.6±15.6 min) was significantly less compared with the THA group (104.8±14.2 min) (P=0.001). Intraoperative blood loss in the traditional surgery group (219.8±21.6 mL) was significantly less compared with the THA group (339.4±29.4 mL) (P=0.001). After treatment, the mean HHS score of the THA group (76.5±9.2 points) was significantly increased when compared with the traditional surgery group (61.4±10.5 points) (P=0.001). Disease recurrence rate in the THA group was significantly reduced compared with the traditional surgery group (P=0.001). The mean quality of life score of the THA group (85.5±6.4 points) was significantly higher than that of the traditional surgery group (73.4±8.8 points) (P=0.001). CONCLUSIONS Compared with closed reduction screw fixation, THA for AVN of the femoral head effectively reduced the length of hospital stay, time to recovery, and achieved an improved clinical outcome.


Assuntos
Artroplastia de Quadril/métodos , Necrose da Cabeça do Fêmur/cirurgia , Adulto , Parafusos Ósseos , China , Feminino , Fraturas do Colo Femoral/cirurgia , Cabeça do Fêmur/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-30932160

RESUMO

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.

5.
Int J Surg ; 46: 14-20, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28797917

RESUMO

OBJECTIVE: We conducted a meta-analysis of RCTs to evaluate the effects of vitamin D supplementation in the prevention of symptom and structural progression of knee OA. METHODS: PubMed, Embase, and Web of Science databases were searched to identify relevant studies. Outcomes included Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain, function, stiffness, tibial cartilage volume, and serum vitamin D3 levels, and adverse events. Results were expressed as weight mean difference (WMD) with 95% confidence interval (CI), and risk ratio (RR) with 95%CI. RESULTS: Four RCTs involving 1136 patients were included in this study. Pooled estimates suggested that vitamin D supplementation was associated with a significant reduction in WOMAC pain, and WOMAC function, but not in WOMAC stiffness. Vitamin D supplementation increased the serum vitamin D3 level, but had no effect on tibial cartilage volume. Subgroup analysis showed that, a daily supplement of more than 2000 IU vitamin D significantly decreased the WOMAC pain and WOMAC function. There was no significant difference in incidence of adverse events between the vitamin D and placebo groups. CONCLUSION: Vitamin D supplementation was effective in improving the WOMAC pain and function in patients with knee OA. However, it had no beneficial effect on the prevention of tibial cartilage loss. Therefore, there is currently a lack of evidence to support the use of vitamin D supplementation in preventing the progression of knee OA.


Assuntos
Suplementos Nutricionais , Osteoartrite do Joelho/terapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Colecalciferol/sangue , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/fisiopatologia , Dor/etiologia , Dor/fisiopatologia , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Tíbia/fisiopatologia , Resultado do Tratamento
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