Ge Gaoran, Yang Sen, Hou Zhenyang, Gan Minfeng, Tao Huaqiang, Zhang Wei, Li Wenming, Wang Zheng, Hao Yuefeng, Gu Ye, Geng Dechun
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
Suzhou Ninth People's Hospital, Suzhou Ninth Hospital affiliated to Soochow University, Suzhou, China.
Front Pharmacol. 2021 Mar 23;12:648969. doi: 10.3389/fphar.2021.648969. eCollection 2021.
Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3'-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/β-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.
绝经后骨质疏松症是一种由于雌激素缺乏导致骨量减少和结构改变的疾病，最终可导致疼痛加剧和骨折风险增加。导致成骨细胞活化减少和骨形成受抑制的慢性炎症微环境是引发骨质疏松症的一个重要病理因素。茶黄素-3,3'-双没食子酸酯（TFDG）是红茶提取物，具有潜在的抗炎和抗病毒作用。在我们的研究中，通过显微CT分析发现TFDG显著增加了去卵巢（OVX）小鼠的骨量。与OVX小鼠相比，TFDG减少了促炎细胞因子的释放，增加了成骨标志物的表达。实验表明，TFDG可在炎症环境中促进成骨细胞的形成并增强其矿化能力。在此过程中，TFDG激活了被TNF-α抑制的MAPK、Wnt/β-连环蛋白和BMP/Smad信号通路，进而促进包括Runx2和Osterix在内的成骨相关因子的转录，最终促进成骨细胞的分化和成熟。总体而言，我们的研究证实TFDG能够在炎症环境下促进成骨细胞分化，增强其矿化能力，并最终增加去卵巢小鼠的骨量。这些结果表明，TFDG可能有潜力成为治疗绝经后骨质疏松症更有效的药物。
