Deepak Vishwa, Kasonga Abe, Kruger Marlena C, Coetzee Magdalena
Department of Physiology, University of Pretoria , Pretoria , South Africa .
Connect Tissue Res. 2015 Jun;56(3):195-203. doi: 10.3109/03008207.2014.989320. Epub 2014 Dec 11.
Bone loss diseases are often associated with increased receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. Compounds that can attenuate RANKL-mediated osteoclast formation are of great biomedical interest. Eugenol, a phenolic constituent of clove oil possesses medicinal properties; however, its anti-osteoclastogenic potential is unexplored hitherto. Here, we found that eugenol dose-dependently inhibited the RANKL-induced multinucleated osteoclast formation and TRAP activity in RAW264.7 macrophages. The underlying molecular mechanisms included the attenuation of RANKL-mediated degradation of IκBα and subsequent activation of NF-κB pathway. Furthermore, increase in phosphorylation and activation of RANKL-induced mitogen-activated protein kinase pathways (MAPK) was perturbed by eugenol. RANKL-induced expression of osteoclast-specific marker genes such as TRAP, cathepsin K (CtsK) and matrix metalloproteinase-9 (MMP-9) was remarkably downregulated by eugenol. These findings provide the first line of evidence that eugenol mediated attenuation of RANKL-induced NF-κB and MAPK pathways could synergistically contribute to the inhibition of osteoclast formation. Eugenol could be developed as therapeutic agent against diseases with excessive osteoclast activity.
骨质流失疾病通常与核因子κB受体活化因子配体（RANKL）诱导的破骨细胞形成增加有关。能够减弱RANKL介导的破骨细胞形成的化合物具有重大的生物医学意义。丁香酚是丁香油中的一种酚类成分，具有药用特性；然而，其抗破骨细胞生成的潜力迄今尚未得到探索。在此，我们发现丁香酚在RAW264.7巨噬细胞中呈剂量依赖性地抑制RANKL诱导的多核破骨细胞形成和抗酒石酸酸性磷酸酶（TRAP）活性。潜在的分子机制包括减弱RANKL介导的IκBα降解以及随后核因子κB（NF-κB）信号通路的激活。此外，丁香酚干扰了RANKL诱导的丝裂原活化蛋白激酶（MAPK）信号通路的磷酸化和激活。丁香酚显著下调了RANKL诱导的破骨细胞特异性标志物基因如TRAP、组织蛋白酶K（CtsK）和基质金属蛋白酶-9（MMP-9）的表达。这些发现提供了首个证据，表明丁香酚介导的RANKL诱导的NF-κB和MAPK信号通路减弱可协同抑制破骨细胞形成。丁香酚可被开发为针对破骨细胞活性过高疾病的治疗药物。
