Programa Multicêntrico de Pós-Graduaçãoem Ciências Fisiológicas, SBFis/UNESP, Brazil; Laboratory of Pharmacology, Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil; Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
Programa Multicêntrico de Pós-Graduaçãoem Ciências Fisiológicas, SBFis/UNESP, Brazil; Laboratory of Biochemistry, Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil; Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
J Ethnopharmacol. 2019 Nov 15;244:112131. doi: 10.1016/j.jep.2019.112131. Epub 2019 Aug 1.
Yerba mate (Ilex paraguariensis) consumption has been associated with beneficial effects on bone health.
The purpose of this study was to evaluate the mechanism by which soluble yerba mate (SYM) stimulates osteoblast differentiation of bone marrow-derived mesenchymal stromal cells (BM-MSCs).
BM-MSCs from male Wistar rats were induced towards osteoblastic differentiation with different concentrations of SYM (10, 20, and 50 μg/mL). Osteoblastic differentiation was evaluated by measuring proliferation rates, alkaline phosphatase activity, MMP-2 activity, mineralization, and gene expression of Runx2, Osterix, β-catenin (Catnb), collagen type I (Col1a1), osteopontin (Opn), osteocalcin (Ocn), bone sialoprotein (Bsp), bone morphogenetic protein-2 (Bmp2), osteoprotegerin (Opg), and Rankl. We also analyzed cytokine production and MAP kinase pathways.
SYM (10 μg/mL) did not show a cytotoxic effect and induced a slight increase in ALP activity; however, a great increase in mineralization was observed. SYM was also able to reduce TNF-α and IL-10 production; increase the expression of transcription factors Runx2, Osterix, and Catnb; and increase matrix proteins Opn, Bsp, Ocn, and Bmp2. We also observed a decrease in intracellular signaling of ERK, JNK, and p38 MAPK, which seemed to be related to the SYM response.
Together, these results help to explain the promoting effect on osteoblast differentiation produced by a low SYM concentration. However, a higher SYM concentration presented deleterious effects, including cytotoxicity, decreased ALP activity, increased cytokine production, decreased bone marker gene expression, increased MAPK signaling, and significant mineralization reduction. In conclusion, our results suggest a concentration-specific direct stimulatory effect of SYM on osteoblastic differentiation in vitro.
饮用马黛茶（Ilex paraguariensis）已被证明对骨骼健康有益。
本研究旨在评估可溶性马黛茶（SYM）刺激骨髓间充质基质细胞（BM-MSCs）成骨分化的机制。
雄性 Wistar 大鼠的 BM-MSCs 用不同浓度的 SYM（10、20 和 50μg/mL）诱导成骨分化。通过测量增殖率、碱性磷酸酶活性、MMP-2 活性、矿化和 Runx2、Osterix、β-连环蛋白（Catnb）、I 型胶原（Col1a1）、骨桥蛋白（Opn）、骨钙素（Ocn）、骨涎蛋白（Bsp）、骨形态发生蛋白-2（Bmp2）、骨保护素（Opg）和核因子 κB 受体激活因子配体（Rankl）的基因表达来评估成骨分化。我们还分析了细胞因子产生和 MAP 激酶途径。
SYM（10μg/mL）没有显示细胞毒性作用，仅轻微增加 ALP 活性，但矿化明显增加。SYM 还能够降低 TNF-α 和 IL-10 的产生；增加转录因子 Runx2、Osterix 和 Catnb 的表达；并增加基质蛋白 Opn、Bsp、Ocn 和 Bmp2 的表达。我们还观察到 ERK、JNK 和 p38 MAPK 细胞内信号的减少，这似乎与 SYM 反应有关。
综上所述，这些结果有助于解释低浓度 SYM 对成骨分化的促进作用。然而，较高浓度的 SYM 表现出有害影响，包括细胞毒性、降低 ALP 活性、增加细胞因子产生、降低骨标志物基因表达、增加 MAPK 信号传导和显著减少矿化。总之，我们的结果表明 SYM 对体外成骨分化具有浓度特异性的直接刺激作用。
