Emodin Regulates Bone Remodeling by Inhibiting Osteoclastogenesis and Stimulating Osteoblast Formation
Emodin Regulates Bone Remodeling by Inhibiting Osteoclastogenesis and Stimulating Osteoblast Formation
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DOI：
10.1002/jbmr.2183
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发表时间：
2014-07-01
影响因子：
6.2
通讯作者：
Oh, Jaemin
中科院分区：
文献类型：
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作者：
Kim, Ju-Young;Cheon, Yoon-Hee;Oh, Jaemin
骨重塑是一种由成骨细胞形成新骨和破骨细胞吸收原有骨基质的生理过程，对维持成年人健康的骨组织至关重要。这个过程中的不平衡会导致各种病理状况，包括骨质疏松症。大黄素是一种在亚洲草药中发现的天然蒽醌衍生物，具有许多有益的药理作用，包括抗癌和抗糖尿病活性。然而，大黄素对成骨细胞和破骨细胞活性的调节作用尚未被研究。我们在这里表明，大黄素是骨质疏松症治疗的潜在靶点，因为用大黄素治疗可以增强成骨细胞分化和骨生长，抑制破骨细胞分化和骨吸收。在本研究中，大黄素通过抑制RANKL诱导的NF-kappa B、c-Fos和NFATc1的表达，抑制核因子κ B受体激活因子（NF-kappa B）配体（RANKL）诱导的骨髓巨噬细胞（BMMs）破骨细胞分化和成熟破骨细胞的骨吸收活性。大黄素还能提高小鼠颅骨初代成骨细胞ALP、茜素红矿化活性和Runx2、骨钙素（OCN）、ALP等成骨基因标记的表达，激活p38-Runx2通路，促进成骨细胞分化。此外，在基于微计算机断层扫描和股骨组织学分析的小鼠颅骨骨形成模型中，用大黄素处理的小鼠显示脂多糖（LPS）诱导的骨侵蚀明显减弱，骨形成活性增加。我们的研究结果揭示了大黄素在骨重塑中的新功能，并强调了其作为治疗骨质疏松症的治疗药物的潜力，该药物可以促进骨合成代谢活性并抑制破骨细胞分化。(C) 2014年美国骨与矿物研究学会。
Bone remodeling, a physiological process in which new bone is formed by osteoblasts and the preexisting bone matrix is resorbed by osteoclasts, is vital for the maintenance of healthy bone tissue in adult humans. Imbalances in this process can cause various pathological conditions, including osteoporosis. Emodin, a naturally occurring anthraquinone derivative found in Asian herbal medicines, has numerous beneficial pharmacologic effects, including anticancer and antidiabetic activities. However, the effect of emodin on the regulation of osteoblast and osteoclast activity has not yet been investigated. We show here that emodin is a potential target for osteoporosis therapeutics, as treatment with this agent enhances osteoblast differentiation and bone growth and suppresses osteoclast differentiation and bone resorption. In this study, emodin suppressed receptor activator of nuclear factor-kappa B (NF-kappa B) ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages (BMMs) and the bone-resorbing activity of mature osteoclasts by inhibiting RANKL-induced NF-kappa B, c-Fos, and NFATc1 expression. Emodin also increased ALP, Alizarin Red-mineralization activity, and the expression of osteoblastogenic genemarkers, such as Runx2, osteocalcin (OCN), and ALP in mouse calvarial primary osteoblasts, as well as activated the p38-Runx2 pathway, which enhanced osteoblast differentiation. Moreover, mice treated with emodin showed marked attenuation of lipopolysaccharide (LPS)-induced bone erosion and increased bone-forming activity in a mouse calvarial bone formation model based on micro-computed tomography and histologic analysis of femurs. Our findings reveal a novel function for emodin in bone remodeling, and highlight its potential for use as a therapeutic agent in the treatment of osteoporosis that promotes bone anabolic activity and inhibits osteoclast differentiation. (C) 2014 American Society for Bone and Mineral Research.