Dual Role of Cyanidin-3-glucoside on the Differentiation of Bone Cells
Dual Role of Cyanidin-3-glucoside on the Differentiation of Bone Cells
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DOI：
10.1177/0022034515604620
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发表时间：
2015-12-01
影响因子：
7.6
通讯作者：
Lee, S. H.
中科院分区：
文献类型：
--
作者：
Park, K. H.;Gu, D. R.;Lee, S. H.
矢车菊素-3-葡萄糖苷（C3 G）是水溶性植物花色素苷的主要成分之一。最近的研究表明，C3 G在各种条件下，包括癌症的化学预防和化疗活性，但C3 G对破骨细胞和成骨细胞分化的确切影响仍不清楚。本研究旨在探讨C3 G在骨相关细胞分化中的作用及其机制。C3 G以剂量依赖性方式抑制核因子κ B受体激活剂配体（RANKL）介导的破骨细胞分化和形成，并下调破骨细胞分化标志物基因的表达。C3 G预处理显著降低了破骨细胞前体细胞中RANKL对细胞外信号调节激酶、c-Jun N-末端激酶和p38丝裂原激活激酶的诱导激活。此外，C3 G显着抑制c-Fos和活化的T细胞的核因子，胞质1，这是破骨细胞分化和活化的重要转录因子的表达。骨髓细胞和颅骨来源的成骨细胞共培养中破骨细胞的形成也被C3 G处理抑制，尽管成骨细胞上巨噬细胞集落刺激因子和RANKL（破骨细胞分化和形成的主要因子）和骨保护素（RANKL的诱饵受体）的表达不受影响。因此，C3 G对破骨细胞生成的抑制作用特异性针对破骨细胞而不是成骨细胞。此外，成骨细胞分化标志基因的表达水平分析和茜素红染色显示，成骨细胞分化和基质形成后C3 G处理增加。总之，这些结果强烈表明，C3 G在骨代谢中具有双重作用，作为破骨细胞分化的有效抑制剂，但也作为成骨细胞分化的激活剂。因此，C3 G可用作骨质疏松症、类风湿性关节炎和牙周炎等骨相关疾病的有效预防或治疗剂。
Cyanidin-3-glucoside (C3G) is one of the major components of anthocyanin, a water-soluble phytochemical. Recent studies demonstrated the chemopreventive and chemotherapeutic activities of C3G in various conditions, including cancer, although the precise effects of C3G on osteoclast and osteoblast differentiation remain unclear. Here, we investigated the role of C3G in the differentiation of bone-associated cells and its underlying mechanism. C3G inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation and formation in a dose-dependent manner and downregulated the expression of osteoclast differentiation marker genes. Pretreatment with C3G considerably reduced the induction of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated kinases activation by RANKL in osteoclast precursor cells. Furthermore, C3G dramatically inhibited the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1, which are important transcription factors for osteoclast differentiation and activation. The formation of osteoclasts in coculture of bone marrow cells and calvaria-derived osteoblasts was also inhibited by C3G treatment, although the expression of macrophage colony-stimulating factor and RANKL (master factors for osteoclast differentiation and formation) and osteoprotegerin (a decoy receptor for RANKL) on osteoblasts was unaffected. The inhibitory effect of C3G on osteoclastogenesis is therefore targeted specifically to osteoclasts but not osteoblasts. Moreover, analysis of the expression levels of osteoblast differentiation marker genes and alizarin red staining showed that osteoblast differentiation and matrix formation increased after C3G treatment. Taken together, these results strongly suggest that C3G has a dual role in bone metabolism, as an effective inhibitor of osteoclast differentiation but also as an activator of osteoblast differentiation. Therefore, C3G may be used as a potent preventive or therapeutic agent for bone-related diseases, such as osteoporosis, rheumatoid arthritis, and periodontitis.