Long non-coding RNA KCNQ1OT1 promotes cell viability and migration as well as inhibiting degradation of CHON-001 cells by regulating miR-126-5p/TRPS1 axis

Abstract Background: Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells. Methods: Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p. Results: Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells. Conclusions: Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.

Study on the protective mechanism of autophagy on cartilage by magnesium sulfate / 中国修复重建外科杂志

Objective: To investigate the mechanism of magnesium sulfate in protecting rabbit cartilage by initiating autophagy. Methods: Twenty-four adult female New Zealand rabbits were used to prepare post-traumatic osteoarthritis (PTOA) models by anterior cruciate ligament transection. Then, the PTOA models were randomly divided into PTOA group, distilled water group, and magnesium sulfate group, with 8 rabbits in each group. Immediately after operation, the distilled water group and the magnesium sulfate group were injected with 0.5 mL distilled water and 20 mmol/L magnesium sulfate solution in the joint cavity 3 times a week for 4 weeks, respectively. The PTOA group was not treated. The general condition of the animals was observed after operation. After 4 weeks, the expressions of tumor necrosis factor α (TNF-α) and collagen typeⅡ in the joint fluid and the expression of collagen type Ⅱ in venous blood were detected by ELISA assay. The protein expressions of transient receptor potential channel vanilloid 5 (TRPV5) and microtubule associated protein 1 light chain 3 (LC3; LC3-Ⅱ/LC3-Ⅰ) in femoral cartilage were detected by Western blot. The mRNA expressions of interleukin 1β (IL-1β), TNF-α, matrix metalloproteinases 3 (MMP-3) in synovial tissue and collagen type Ⅱ, Aggrecan (AGN), SOX9 in cartilage tissue were detected by real-time fluorescence quantitative PCR. Cartilage tissue sections were stained with HE staining, Masson staining, and Alcian blue staining and scored according to the modified histological osteoarthritis (OA) score. Results: All animals survived until the experiment was completed. Compared with the other two groups, the expression of TNF-α in joint effusion and collagen type Ⅱ in joint effusion and venous blood were decreased in magnesium sulfate group; the protein expression of TRPV5 decreased, and the ratio of LC3-Ⅱ/LC3-Ⅰ increased significantly; the mRNA expressions of IL-1β, TNF-α, and MMP-3 in synovial tissue were decreased, and the mRNA expressions of collagen type Ⅱ, AGN, and SOX9 in cartilage tissue were increased; OA scores also decreased significantly. All differences were statistically significant ( P0.05). Conclusion: Intra-articular injection of magnesium sulfate can reduce intra-articular inflammation, reduce the loss of collagen type Ⅱ and AGN, and is beneficial to cartilage regeneration in rabbits. The mechanism may be related to the initiation of chondroautophagy by inhibiting the calcium channel TRPV5.

The Mid-Term Result after Osteosynthesis of Intra-Articular Fractures of Distal Femur

PURPOSE: This study was to evaluate the radiological and clinical mid-term results and the presence of post-traumatic osteoarthritis after osteosynthesis in patients under the age of 50 years undergoing osteosynthesis for distal femur intra-articular fractures (AO/OTA 33-B & C) from high-energy trauma. MATERIALS AND METHODS: Between January 2008 and January 2013, a total of twenty-one patients with more than three years of follow-up were enrolled. Recovery of the alignment of the lower extremity, union period, and the presence of post-traumatic osteoarthritis were confirmed by follow-up radiographs. Clinically, the range of motion, pain on fracture lesion, and Knee Society score (KSS) were evaluated. RESULTS: The average duration of union was 18.2 weeks (10-28 weeks), and the alignment of the lower extremity was within normal range in all patients. Seven patients showed post-traumatic osteoarthritis at the final follow-up after more than three years. The presence of post-traumatic osteoarthritis was associated with the classification of fractures, coronal plane fracture, and age. The average range of motion, knee score among KSS, and function score at the last follow-up were 128.7°, 86.1, and 85.1, all showing a greater improvement when compared with the one-year follow-up scores. CONCLUSION: The mid-term result was radiologically and clinically satisfactory. Furthermore, only 33.3% of patients showed a slight progress of post-traumatic osteoarthritis, which critically effects the prognosis.

Resultado a largo plazo del tratamiento quirúrgico de las fracturas del tobillo. (5 años de seguimiento) / Long-term outcome of surgical treatment of ankle fractures. (5 years follow up)

Antecedentes: Algunos autores documentan alteración funcional con molestias asociadas en un importante número de pacientes a largo plazo luego de cirugía en fracturas de tobillo. Lesiones iniciales de cartílago, así como reducción primaria deficiente predispone a resultados desfavorables. Método: serie clínica. Evaluación funcional de fracturas de tobillo luego de cinco años de la cirugía. Se utilizó las escalas de Olerud y Molander, y Baird para evaluación. La prueba Chi2 se utilizó para inferencia estadística. Resultados: 24 pacientes, 15 hombres y 9 mujeres; La edad promedio fue 28 años (16-68 años). Hubo una asociación directamente proporcional entre dolor y limitación laboral (X2: p <0.05); igualmente el dolor estuvo relacionado de manera directa con los puntajes más bajos de las escalas (X2: p <0.05). A mayor deterioro radiológico mayor intensidad de dolor (X2: p <0.05). Hubo una asociación directa entre reducción inicial inadecuada y deterioro radiológico (X2: p <0.05). 75% resultados satisfactorios. Conclusiones: El dolor fue el síntoma capital que condicionó el resultado final. El deterioro radiológico se asoció mayormente a mala reducción inicial. Un importante número de pacientes presentan algún grado de deterioro de la función 5 años después de la cirugía, aun con buena reducción inicial(AU)

Background: Some authors document discomfort associated with functional impairment in a significant number of patients after long-term surgery on ankle fractures. Initial cartilage injuries and poor primary reduction predisposes unfavorable results. Method: clinical series. Functional assessment of ankle fractures after five years of surgery. We used scales Olerud Molander, and Baird for evaluation. The Chi2 test was used for statistical inference. Results:. 24 patients, 15 males and 9 women, mean age was 28 years (16-68 years). There was an directly proportional association between pain and labor limitation (X2: p <0.05), and also the pain was related directly with the lowest scores of the scales (X2: p <0.05). A further deterioration radiological, greater pain (X2: p <0.05). There was a direct association between inadequate initial reduction and radiological deterioration (X2: p <0.05). Conclusions. Pain was the main symptom that determined the outcome. The radiological deterioration was associated mostly with poor initial reduction. A significant number of patients have some degree of impaired function 5 years after surgery, even with good initial reduction. 75% of patients had satisfactory results(AU)

Operative Treatment of the Ankle Fracture with Dislocation: Minimum 2-year Follow Up Results / 대한족부족관절학회지

PURPOSE: In previous study, the frequency of osteoarthritis and discomfort were high in ankle fracture-dislocation but detail results about ankle fracture-dislocation has rarely been investigated. In this study, we retrospectively analyze the outcome of the operative treatment of ankle fracture with dislocation for over-2 years follow up. MATERIALS AND METHODS: There were 47 cases of ankle fracture-dislocation in our hospital from March 2007 to May 2010. We investigated 20 patients who underwent operation and were possible for over-2 years follow up. The result was estimated with the direction of dislocation, fracture type, the time of bone union and post-traumatic osteoarthritis with plain radiologic images. In clinical assessment, we statistically evaluated the function and pain through AOFAS score and Olerud & Molander scoring system. RESULTS: By Lauge-Hansen classification, there were 13 cases(65%) of pronation-external rotation and 6 cases(30%) of supination-external rotation, 1 case(5%) of supination-adduction. AOFAS score was 85.5, and Olerud & Molander score was"excellent" in 8 cases, "good" in 5 cases, "fair" in 3 cases and "poor" in 4 cases. Postoperative complications in 4 cases revealed post-traumatic arthritis. All kinds of lateral dislocation of ankle fracture was 15 cases and the most common. Of these, all 3 cases, anterolateral dislocation showed post-traumatic osteoarthritis. CONCLUSION: In ankle fracture-dislocation, post-traumatic osteoarthritis occurred in 4 of 20 patient(20%). Especially, the possibility of post-traumatic osteoarthritis was more in cases of anterolateral or lateral dislocation. So, it must be needed that deliberate examination, for example, preoperative MRI and sufficient explanation to patient. Also, we have to follow up the patients carefully.