RESUMEN
Highmobility group box chromosomal protein (HMGB1) contributes to osteoarthritis (OA) by modulating various oxidative, inflammatory and apoptotic signaling pathways. The effect of chrysin (CH), a natural plant flavonoid, and its functional interaction with HMGB1, was investigated in a chondrocyte model of OA. Human chondrocytes were pretreated with CH, and then subsequently treated with IL1ß to induce the formation of chondrocytes similar to those found in OA joints. Next, the expression level of HMGB1 was determined by immunofluorescence and western blot analysis. Additionally, inflammatory factor expression was measured by ELISA, and cell apoptosis was analyzed with flow cytometry. To further explore the effects of CH, HMGB1 expression was silenced following CH treatment with small interfering (si)RNA. The results demonstrated that CH inhibited cell apoptosis, dosedependently reduced matrix metalloproteinase (MMP) 13, collagenase and IL6 expression, and increased collagen α1 (II) chain (COL2A1) expression in human osteoarthritis chondrocytes. These effects of CH were accompanied by decreased HMGB1 expression. Additionally, the expression of MMP13, collagenase, IL6 and COL2A1, as well as apoptosis, was significantly reduced by HMGB1 siRNA. These results demonstrated that HMGB1 is critical for the protective effect of CH on human osteoarthritis chondrocytes, including cell apoptosis and inflammatory factor inhibition, which suggests that CH may have potential therapeutic effect in treating OA by protecting human osteoarthritis chondrocytes via HMGB1 suppression.
Asunto(s)
Condrocitos/efectos de los fármacos , Flavonoides/farmacología , Proteína HMGB1/metabolismo , Mediadores de Inflamación/metabolismo , Osteoartritis/tratamiento farmacológico , Sustancias Protectoras/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Condrocitos/metabolismo , Colagenasas/metabolismo , Humanos , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Osteoartritis/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Osteoarthritis (OA) is one of the most common chronic degenerative diseases characterized by deterioration of articular cartilage. Many studies have demonstrated the role of microRNAs (miRNAs) in OA, but the role of miR-320a in OA remains elusive. The aim of this study was to identify the protective role of miR-320a in OA cartilage degeneration by regulating the expression of BMI-1 and RUNX-2 proteins in chondrocytes. Normal and OA chondrocytes obtained from patients were cultured in vitro. The chondrocytes (both normal and OA) were transfected with miR-320a inhibitor to investigate the effects of miR-320a on chondrocyte proliferation, and to identify the miR-320a target proteins. The results indicated that miR-320a expression was significantly higher (P<0.05) in OA chondrocytes than in normal chondrocytes. Inhibition of miR-320a effectively enhanced chondrocyte cell viability in vitro in a time-dependent manner. Inhibition of miR-320a showed a significant decrease (P<0.05) in the secretion of matrix metalloproteinase-13 (MMP-13). Furthermore, miR-320a could regulate the expression levels of BMI-1 and RUNX-2 proteins in OA chondrocytes (P<0.05). The data suggested that miR-320a protected against OA cartilage degeneration and regulated the expression levels of BMI-1 and RUNX2 proteins in chondrocytes. Our study might provide a new insight in the clinical treatment of OA.
Asunto(s)
Cartílago Articular/patología , Condrocitos/patología , MicroARNs/genética , Osteoartritis/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Regulación de la Expresión Génica/genética , Humanos , Metaloproteinasa 13 de la Matriz/metabolismo , Osteoartritis/genética , Complejo Represivo Polycomb 1/genética , Factores de TiempoRESUMEN
PURPOSE: In this study, we designed a prospective project to test the hypothesis that acute fourth and fifth carpometacarpal (CMC) fracture dislocations can be treated conservatively with good restoration of strength, range of motion (ROM), and function, whereas patients with delayed treatment of fourth and fifth CMC fracture dislocations should be treated with open reduction and internal fixation (ORIF). METHODS: We evaluated the results of 20 patients with acute and 6 patients with subacute fourth and fifth CMC fracture dislocations. All 20 acute CMC fracture dislocations were treated conservatively, whereas 3 of the 6 patients with subacute injuries underwent operative intervention. The sensibility, ROM, and grip strength of the hands were tested during 1-year follow-up. The Michigan Hand Outcomes Questionnaire and control radiographs were also taken. RESULTS: All 20 patients with acute CMC fracture dislocations showed good restoration of grip strength, ROM, and function, with an average Michigan Hand Outcomes Questionnaire score of 98 ± 2 at 1-year follow-up. Patients with delayed diagnosis who underwent conservative treatment had noticeable deformity of their injured hands, pain complaints, limited ROM at the fourth and fifth CMC joints, and decreased grip strength. The 3 patients with delayed diagnosis treated with ORIF showed good restoration of grip strength, ROM, and function. CONCLUSIONS: Patients with acute CMC fracture dislocations can be treated by closed reduction with good restoration of grip strength, ROM, and function. In patients with delayed presentation of CMC fracture dislocations, we recommend ORIF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.