Department of Chemistry and Biochemistry, Laboratory of Bioassays and Cell Dynamics, Institute of Biosciences, Sao Paulo State University - UNESP, Botucatu, São Paulo, Brazil.
Department of Microbiology and Immunology, Institute of Biosciences, Sao Paulo State University - UNESP, Botucatu, São Paulo, Brazil.
J Cell Biochem. 2019 Aug;120(8):13413-13425. doi: 10.1002/jcb.28616. Epub 2019 Mar 27.
Natural molecules, such as flavonoid, are very welcome strategies to modulate bone turnover. This prompted us to comprehend better the effect of silibinin on osteoblast metabolism, mainly considering intracellular pathways able to drive cell adhesion to differentiation. By exploring in vitro approaches, our data show a modulatory effect of the silibinin (200 μg/mL) on the osteoblast intracellular signaling, contributing with decisive pathways governing cell adhesion, differentiation, and further mineralization, recapitulating important stages of osteogenesis. Within the first 24 hours of adhesion (acute stage), osteoblasts respond to silibinin by rearranging their cytoskeleton and start mechanisms responsible to extracellular matrix (ECM) remodeling, which reach intense profile at 28 days of treatment (chronic stage) by favoring matrix metalloproteinases (MMPs-2, and -9) activities, concomitant to mineralizing phenotype. Importantly, silibinin seems to reprogram genes related to inflammatory landscape and significantly upmodulating osteoprotegerin (>25 fold-changes), signaling molecule involved with osteoclastogenesis. Altogether, our results show for the first time that silibinin drives in vitro osteoblast differentiation by requiring specific intracellular signaling. In conjunction, this molecular landscape contributes to understand the effect of silibinin on osteoblasts performance and open novel therapeutic possibilities to silibinin in bone disorders, such as osteoporosis.
天然分子，如类黄酮，是调节骨转换的非常受欢迎的策略。这促使我们更好地理解水飞蓟宾对成骨细胞代谢的影响，主要考虑能够驱动细胞黏附分化的细胞内途径。通过探索体外方法，我们的数据显示水飞蓟宾（200μg/ml）对成骨细胞细胞内信号有调节作用，有助于控制细胞黏附、分化和进一步矿化的决定性途径，再现成骨的重要阶段。在黏附的最初 24 小时（急性期），成骨细胞通过重排细胞骨架对水飞蓟宾做出反应，并开始负责细胞外基质（ECM）重塑的机制，这些机制在 28 天的治疗（慢性期）达到强烈状态，通过促进基质金属蛋白酶（MMP-2 和 MMP-9）的活性，同时促进矿化表型。重要的是，水飞蓟宾似乎重新编程与炎症景观相关的基因，并显著上调护骨素（>25 倍变化），这是一种与破骨细胞形成有关的信号分子。总的来说，我们的研究结果首次表明，水飞蓟宾通过特定的细胞内信号驱动体外成骨细胞分化。此外，这种分子景观有助于理解水飞蓟宾对成骨细胞性能的影响，并为骨疾病（如骨质疏松症）中水飞蓟宾的治疗提供新的可能性。
