Huang Li, Jin Pan, Lin Xiao, Lin Cuiwu, Zheng Li, Zhao Jinmin
Guangxi Engineering Center for Biomaterials for Tissue and Organ Regeneration, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, P.R. China.
Mol Med Rep. 2017 Mar;15(3):1149-1156. doi: 10.3892/mmr.2017.6142. Epub 2017 Jan 24.
Effective treatments for osteoporosis remain fairly elusive; however, studies have reported that antioxidants may aid in the maintenance of reactive oxygen species at a favorable level, in order to prevent osteoporosis. Gallic acid (GA) and its derivatives are potent antioxidative and anti‑inflammatory agents that affect several biochemical and pharmacological pathways; however, GA is slightly cytotoxic and suppresses cell proliferation. The present study modified GA by the introduction of sulfonamide, in order to obtain a novel compound known as JEZ‑C, and investigated its effects on osteoblasts by measuring cell proliferation, viability, morphology, alkaline phosphatase (ALP) activity, and the expression of relevant osteoblast markers. Results indicated that JEZ‑C may effectively promote osteoblast growth. JEZ‑C increased ALP activity, upregulated the expression of osteogenic‑related genes, including runt‑related transcription factor 2, bone sialoprotein, osteocalcin and alpha‑1 type I collagen, thus indicating that JEZ‑C enhances bone matrix production and mineralization. The recommended range of JEZ‑C concentration is between 6.25x10‑3 and 6.25x10‑1 µg/ml, within which cell growth was promoted compared with the control. Specifically, treatment with 6.25x10‑2 µg/ml JEZ‑C is ideal. These findings may represent a novel approach to cell‑based therapy for the treatment of osteoporosis.
有效的骨质疏松症治疗方法仍然相当难以捉摸；然而，研究报告称抗氧化剂可能有助于将活性氧维持在有利水平，以预防骨质疏松症。没食子酸（GA）及其衍生物是有效的抗氧化和抗炎剂，可影响多种生化和药理途径；然而，GA具有轻微的细胞毒性并抑制细胞增殖。本研究通过引入磺酰胺对GA进行修饰，以获得一种名为JEZ-C的新型化合物，并通过测量细胞增殖、活力、形态、碱性磷酸酶（ALP）活性以及相关成骨细胞标志物的表达来研究其对成骨细胞的影响。结果表明，JEZ-C可能有效地促进成骨细胞生长。JEZ-C增加了ALP活性，上调了包括 runt 相关转录因子2、骨唾液蛋白、骨钙素和α-1 I型胶原在内的成骨相关基因的表达，从而表明JEZ-C增强了骨基质的产生和矿化。JEZ-C的推荐浓度范围为6.25×10⁻³至6.25×10⁻¹μg/ml，在此范围内与对照组相比细胞生长得到促进。具体而言，用6.25×10⁻²μg/ml JEZ-C处理是理想的。这些发现可能代表了一种基于细胞的骨质疏松症治疗新方法。
