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矢车菊素对 RANKL 诱导的破骨细胞分化和融合的双重作用。

Dual Effect of Cyanidin on RANKL-Induced Differentiation and Fusion of Osteoclasts.

机构信息

Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing, China.

National & Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China.

出版信息

J Cell Physiol. 2016 Mar;231(3):558-67. doi: 10.1002/jcp.24916.

DOI:10.1002/jcp.24916
PMID:25545964
Abstract

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells derived from hematopoietic stem cells (HSCs) or monocyte/macrophage progenitor cells and formed by osteoclasts precursors (OCPs) fusion. Cyanidin is an anthocyanin widely distributed in food diet with novel antioxidant activity. However, the effect of cyanidin on osteoclasts is still unknown. We investigated the effect of cyanidin on RANKL-induced osteoclasts differentiation and cell fusion. The results showed that cyanidin had a dual effect on RANKL-induced osteoclastogenesis. Lower dosage of cyanidin (< 1 µg/ml) has a promoting effect on osteoclastogenesis while higher dosage of cyanidin (> 10 µg/ml) has an inhibitory effect. Fusogenic genes like CD9, ATP6v0d2, DC-STAMP, OC-STAMP, and osteoclasts related genes like NFATc1, mitf, and c-fos were all regulated by cyanidin consistent to its dual effect. Further exploration showed that low concentration of cyanidin could increase osteoclasts fusion whereas higher dosage of cyanidin lead to the increase of LXR-β expression and activation which is suppressive to osteoclasts differentiaton. All these results showed that cyanidin exhibits therapeutic potential in prevention of osteoclasts related bone disorders.

摘要

骨稳态是通过成骨细胞骨形成和破骨细胞骨吸收之间的平衡来维持的。破骨细胞是来源于造血干细胞(HSCs)或单核细胞/巨噬细胞祖细胞的多核细胞,由破骨细胞前体(OCPs)融合形成。矢车菊素是一种广泛存在于饮食中的花色苷,具有新颖的抗氧化活性。然而,矢车菊素对破骨细胞的影响尚不清楚。我们研究了矢车菊素对 RANKL 诱导的破骨细胞分化和细胞融合的影响。结果表明,矢车菊素对 RANKL 诱导的破骨细胞生成具有双重作用。较低剂量的矢车菊素(<1μg/ml)对破骨细胞生成有促进作用,而较高剂量的矢车菊素(>10μg/ml)则有抑制作用。融合基因,如 CD9、ATP6v0d2、DC-STAMP、OC-STAMP 和破骨细胞相关基因,如 NFATc1、mitf 和 c-fos,都受矢车菊素的调节,与其双重作用一致。进一步的探索表明,低浓度的矢车菊素可以增加破骨细胞的融合,而较高剂量的矢车菊素则导致 LXR-β表达和激活的增加,这对破骨细胞分化有抑制作用。所有这些结果表明,矢车菊素在预防破骨细胞相关的骨骼疾病方面具有治疗潜力。

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