ABSTRACT
Osteoporosis is a metabolic bone illness characterized by low bone density and a high risk of fracture. It is estimated that there are >60 million individuals in China suffering from this disease, which highlights an urgent requirement for the development of novel and safe drugs for the long-term treatment of osteoporosis. MicroRNAs (miRNAs/miRs) have previously been identified as critical regulators in the progression of osteoporosis. As an intronic miRNA, miR-27b enhances the osteoblastic differentiation of stem cells from the bone marrow and the maxillary sinus membrane. However, the mechanism underlying miR-27b in osteoporosis remains to be elucidated. In the present study, MC3T3-E1 pre-osteoblasts were treated with dexamethasone (DEX) to establish an in vitro model of osteoporosis. The results of the present study demonstrated that DEX treatment markedly inhibited the viability of MC3T3-E1 cells, and downregulated the expression level of miR-27b. The results of reverse transcription-quantitative PCR, western blotting and dual-luciferase assays revealed that miR-27b directly regulated and suppressed the expression of peroxisome proliferator-activated receptor γ2 (PPARγ2) in MC3T3-E1 cells. Furthermore, overexpression of miR-27b by transfection of cells with miR-27b mimic attenuated DEX-mediated inhibition of cell viability, alkaline phosphatase (ALP) activity and the expression levels of bone morphogenetic protein-2 (BMP2), runt-related protein 2 (Runx2) and osteocalcin (OCN). The results of the present study indicated that miR-27b alleviated DEX-inhibited proliferation and osteoblastic differentiation. Moreover, miR-27b knockdown repressed MC3T3-E1 cell viability, ALP activity and protein levels of BMP2, Runx2 and OCN. However, these effects were abrogated by small interfering RNA-mediated PPARγ2 silencing. In conclusion, the results of the present study demonstrated that miR-27b attenuated DEX-inhibited proliferation and osteoblastic differentiation in MC3T3-E1 pre-osteoblasts by targeting PPARγ2.
ABSTRACT
Several studies have demonstrated that polymorphisms within the IL-1 gene cluster are associated with the risk of ankylosing spondylitis (AS) in different populations. In this study, we desired to know whether IL1R1, a gene located in the IL-1 gene cluster, is a susceptible gene for AS in a Northwest Chinese Han population. The Sequenom MassARRAY assay technique was used to determine the genotype of 267 AS patients and 297 controls from Northwest China. Genotype and allele distributions of the investigated IL1R1 variants (rs10490571, rs12712127, rs956730, rs3917225, and rs3917318) were compared among the cases and controls using Chi-square/Fisher's exact tests. In addition, the associations of these polymorphisms with AS risk were also assessed under dominant, recessive, and additive genetic models using PLINK software. We found the minor G allele of rs3917225 was associated with an increased risk of AS (OR=1.39, 95% CI: 1.09-1.77, P=0.007). Significant association was also detected for rs956730 under the dominant model (OR=0.54, 95% CI: 0.30-0.96, P=0.032) and the additive model (OR=0.55, 95% CI: 0.34-0.90, P=0.016), adjusting for age and gender. This study is the first to demonstrate the significant association between IL1R1 polymorphisms and AS susceptibility in a Northwest Chinese Han population.
