Abstract：
Increasing epidemiological evidence has shown that PM2.5 exposure is significantly associated with the occurrence of osteoporosis. It has been well demonstrated that PM2.5 exposure enhanced the differentiation and function of osteoclasts by indirectly causing chronic inflammation, while the mechanism in osteoblasts remains unclear. In our study, toxic effects were evaluated by direct exposure of 20-80 μg/ml PM2.5 to MC3T3-E1 cells and BMSCs. The results showed that PM2.5 exposure did not affect cell viability via proliferation and apoptosis, but significantly inhibited osteoblast differentiation in a dose-dependent manner. Osteogenic transcription factors Runx2 and Sp7 and other biomarkers Alp and Ocn decreased after PM2.5 exposure. RNA-seq revealed TGF-β signaling was involved in PM2.5 exposure inhibited osteoblast differentiation, which led to P-Smad1/5 and P-Smad2 reduction in the nucleus by increasing the ubiquitination and degradation of Smad4. At last, the inflammation response increased in MC3T3-E1 cells with PM2.5 exposure. Moreover, the mRNA levels of Mmp9 increased in bone marrow-derived macrophage cells treated with the conditional medium collected from MC3T3-E1 cells exposed to PM2.5. Overall, these results indicated that PM2.5 exposure inhibits osteoblast differentiation and concurrently increases the maturation of osteoclasts. Our study provides in-depth mechanistic insights into the direct impact of PM2.5 exposure on osteoblast, which would indicate the unrecognized role of PM2.5 on osteoporosis.
摘要：
越来越多的流行病学证据表明，PM2.5暴露与骨质疏松症的发生显着相关。已经充分证明，PM2.5暴露通过间接引起慢性炎症，增强破骨细胞的分化和功能，而成骨细胞的机制尚不清楚。在我们的研究中,通过直接暴露20-80μg/mlPM2.5对MC3T3-E1细胞和BMSCs的毒性评价。结果表明，PM2.5暴露不会通过增殖和凋亡影响细胞活力，但以剂量依赖性方式显著抑制成骨细胞分化。PM2.5暴露后，成骨转录因子Runx2和Sp7以及其他生物标志物Alp和Ocn降低。RNA-seq显示TGF-β信号参与PM2.5暴露抑制成骨细胞分化,通过增加Smad4的泛素化和降解导致核中P-Smad1/5和P-Smad2的减少。最后,PM2.5暴露后，MC3T3-E1细胞的炎症反应增加。此外，在用条件培养基处理的骨髓源性巨噬细胞中,Mmp9的mRNA水平升高,所述条件培养基是从暴露于PM2.5的MC3T3-E1细胞中收集的.总的来说,这些结果表明，PM2.5暴露抑制了成骨细胞的分化，同时增加了破骨细胞的成熟。我们的研究为PM2.5暴露对成骨细胞的直接影响提供了深入的机制见解，这将表明PM2.5对骨质疏松症的作用尚未被识别。
