Objective Osteoporosis is a progressive systemic skeletal disorder. Multiple profiling studies have contributed to characterizing biomarkers and therapeutic targets for osteoporosis. However, due to the limitation of the platform of miRNA sequencing, only a part of miRNA can be sequenced based on one platform. Materials and methods In this study, we performed miRNA sequencing in osteoporosis bone samples based on a novel platform Illumina Hiseq 2500. Bioinformatics analysis was performed to construct osteoporosis-related competing endogenous RNA (ceRNA) networks. Gene interference and osteogenic induction were used to examine the effect of identified ceRNA networks on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (HBMSCs). Results miR-1303 was lowly expressed, while cochlin (COCH) and KCNMA1-AS1 were highly expressed in the osteoporosis subjects. COCH knockdown improved the osteogenic differentiation of HBMSCs. Meanwhile, COCH inhibition compensated for the suppression of osteogenic differentiation of HBMSCs by miR-1303 knockdown. Further, KCNMA1-AS1 knockdown promoted osteogenic differentiation of HBMSCs through downregulating COCH by sponging miR-1303. Conclusions Our findings suggest that the KCNMA1-AS1/miR-1303/COCH axis is a promising biomarker and therapeutic target for osteoporosis.

BackgroundPrevious studies have not provided a consensus on the effect of serum 25-hydroxyvitamin D [25(OH)D] on osteoarthritis (OA). We aimed to evaluate the association using a large, nationally representative sample.MethodsThe cross-sectional data were obtained from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES). Individuals aged ≥40 years who had information of serum 25(OH)D, self-report OA, and related covariates were included. Multivariable logistic regression analysis was employed to assess the association between serum 25(OH)D and osteoarthritis.ResultsAmong the 21,334 participants included (weighted mean age, 56.9 years; 48.5% men), the proportion of participants with high serum 25(OH)D concentrations (≥100 nmol/L) increased significantly from 4.2% in 2001–2006 to 18.8% in 2013–2018. Higher serum 25(OH)D levels were associated with more osteoarthritis prevalence in fully adjusted model (odd ratio [OR] 1.25 [95% CI: 1.10, 1.43] for the 50–75 nmol/L group; OR 1.62 [95% CI: 1.42, 1.85] for the 75–100 nmol/L group; OR 1.91 [95% CI: 1.59, 2.30] for the ≥100 nmol/L group; with <50 nmol/L group as the reference) (p < 0.001 for trend). The association was consistent across several sensitivity analyses, including propensity score methods and excluding participants who had received vitamin D supplement. In subgroup analysis, the OR for the association increased significantly with body mass index (BMI) (BMI < 25 kg/m2, 1.01 [95% CI: 1.04, 1.08]; BMI 25–30 kg/m2, 1.05 [95% CI: 1.01, 1.08]; BMI ≥ 30 kg/m2, 1.10 [95% CI: 1.06, 1.13]; p = 0.004 for interaction).ConclusionThere was a positive correlation between serum 25(OH)D and osteoarthritis with a possible modification by BMI. Our finding raises concerns about the potential adverse effects of high serum 25(OH)D on osteoarthritis, particularly among obese individuals. More well-designed studies are still needed to validate our findings in future.