Dysregulated MiR-3150a-3p Promotes Lumbar Intervertebral Disc Degeneration by Targeting Aggrecan.

BACKGROUND/AIMS: Low back pain has become one of the most common musculoskeletal diseases in the world. Studies have shown that intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the mechanisms underlying IDD remain largely unknown. Research over the past decade has suggested critical roles for microRNAs (miRNAs) in natural growth and disease progression. However, it remains poorly understood whether circular RNAs participate in IDD. METHODS: Clinical IDD samples were collected from 20 patients who underwent discectomy. Weighted gene co-expression network analysis was used to identify the co-expression miRNA network modules (highly co-expressed clusters of miRNAs) that were associated with IDD grade. RESULTS: miR-3150a-3p was the most significantly up-regulated miRNA in module "Blue." Notably, aggrecan (ACAN) was identified as a direct target gene of miR-3150a-3p and ACAN expression was regulated by miR-3150a-3p. Overexpression of miR-3150a-3p decreased ACAN expression in nucleus pulposus cells, whereas inhibition of miR-3150a-3p increased ACAN expression. In addition, ACAN expression was negatively correlated with IDD grade. CONCLUSION: Our study suggests that the reduction of ACAN expression induced by the upregulation of miR-3150a-3p might participate in the development of IDD.

Cryptococcosis of lumbar vertebra in a patient with rheumatoid arthritis and scleroderma: case report and literature review.

BACKGROUND: Although cryptococcosis mainly occurs in the central nervous system and lungs in immunocompromised hosts, it can involve any body site or structure. Here we report the first case of primary cryptococcosis of a lumbar vertebra without involvement of the central nervous system or lungs in a relatively immunocompromised individual with rheumatoid arthritis and scleroderma. CASE PRESENTATION: A 40-year-old Chinese woman with rheumatoid arthritis diagnosed 1 year beforehand and with a subsequent diagnosis of scleroderma was found to have an isolated cryptococcal infection of the fourth lumbar vertebra. Her main complaints were severe low back and left leg pain. Cryptococcosis was diagnosed by CT-guided needle biopsy and microbiological confirmation; however, serum cryptococcal antigen titer was negative. After 3 months of antifungal therapy with fluconazole the patient developed symptoms and signs of scleroderma, which was confirmed on laboratory tests. After taking fluconazole for 6 months, the progressive destruction of the lumbar vertebral body had halted and the size of an adjacent paravertebral mass had decreased substantially. On discharge symptoms had resolved and at an annual follow-up there was no evidence of recurrence on the basis of symptoms, signs or imaging investigations. CONCLUSION: Although cryptococcosis of the lumbar vertebra is extremely rare, it should be considered in the differential diagnosis for patients with lumbar vertebral masses to avoid missed diagnosis, misdiagnosis and diagnostic delay. Early treatment with antifungals proved to be a satisfactory alternative to surgery in this relatively immunocompromised patient. Any residual spinal instability can be treated later, once the infection has resolved.

Analysis on the risk factors of second fracture in osteoporosis-related fractures.

OBJECTIVE: To explore the clinical characteristics and risk factors of refracture in patients suffering from osteoporosis-related fractures as well as effective interventions. METHODS: From January 2006 to January 2008, both out-patients and in-patients in our hospital who were over 50 years old and suffered from osteoporosis-related fractures were selected for this research. They were divided into fracture group and refracture group. The refracture rate was followed up for 2 years, during which 11 patients developed refracture, thus were included in the refracture group. Therefore, 273 patients, 225 first-fracture cases, aged (67.7+/-8.5) years, and 48 refracture cases, aged (72.7+/-9.5) years, were included in this study. General data including age and sex, fracture types, femoral neck bone mineral density (BMD) T-scores tested by dual-energy X-rays absorptiometry (DEXA), Charlson index, time-frame between two fractures as well as mobility skill assessment were collected and analyzed by single-factor and multivariate statistical methods. RESULTS: Females accounted for 70.2% of the fracture group and 77.1% of the refracture group. The most common refracture type was vertebral fracture for the first time and femoral neck fracture for the second time during the follow-up. The second fracture happened 3.7 years after the first one on average. The refracture rate was 2.12% within one year, and 4.66% within two years. Risk factors for a second fracture in osteoporotic fracture patients included age (larger than 75 years, HR equal to 1.23, 95%CI 1.18-1.29; larger than 85 years, HR equal to 1.68, 95% CI 1.60-1.76), female sex (HR equal to 1.36, 95%CI 1.32-1.40), prior vertebral fractures (HR equal to 1.62, 95%CI 1.01-2.07), prior hip fractures (HR equal to 1.27, 95%CI 0.89-2.42), BMD T-score less than -3.5 (HR equal to 1.38, 95%CI 1.17-1.72) and weakened motor skills (HR equal to 1.27, 95%CI 1.09-1.40). CONCLUSIONS: The risks of second fracture among patients with initial brittle fracture are substantial. There is adequate time between the first and second fractures for interventions to reduce the risks of refracture, especially for the old women with a vertebral or hip fracture. Medication, motor functional rehabilitation and fall-down prevention training are helpful.

MicroRNA-497 inhibits cell proliferation, migration, and invasion by targeting AMOT in human osteosarcoma cells.

MicroRNAs (miRNAs) have a role in the development and progression of human malignancy. The expression of miR-497 is decreased in malignant tumors, which suggests a role for miR-497 as a tumor suppressor. Angiomotin is encoded by the AMOT gene, which is a target for miR-497. Angiomotin has a role in angiogenesis, cell proliferation, and invasion in human malignancies, including osteosarcoma. However, the role of miR-497 in human osteosarcoma is unknown. This preliminary study included human osteosarcoma tissues and normal tissues from 20 patients, the osteosarcoma cell lines, MG-63, SAOS-2, U-2 OS, and the human osteoblast cell line hFOB (OB3). Western blots for angiomotin and quantitative real-time polymerase chain reaction for the expression of miR-497 and AMOT were performed. Knockdown studies were performed using RNA interference and transfection studies used miR-497 mimics. Quantitative cell migration assays were performed, and cell apoptosis was studied by flow cytometry. Osteosarcoma cells and cell lines showed reduced expression of miR-497 and increased expression of angiomotin. Transfection of osteosarcoma cells with miR-497 mimics suppressed the expression of angiomotin. Results from a dual-luciferase reporter system supported AMOT as a direct target gene of miR-497. Knockdown of AMOT using RNA interference resulted in inhibition of osteosarcoma cell proliferation, migration, and invasion. These preliminary studies support a role for miR-497 as a suppressor of AMOT gene expression in human osteosarcoma cells, resulting in suppression of tumor cell proliferation and invasion. Further studies are recommended to investigate the role of miR-497 in osteosarcoma and other malignant mesenchymal tumors.