Ang Estabelle S M, Pavlos Nathan J, Chai Lee Y, Qi Ming, Cheng Tak S, Steer James H, Joyce David A, Zheng Ming H, Xu Jiake
Molecular Orthopaedic Laboratory, Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Nedlands, Western Australia, Australia.
J Cell Physiol. 2009 Dec;221(3):642-9. doi: 10.1002/jcp.21898.
Receptor activator NF-kappaB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation and survival. Caffeic acid phenethyl ester (CAPE), a natural NF-kappaB inhibitor from honeybee propolis has been shown to have anti-tumor and anti-inflammatory properties. In this study, we investigated the effect of CAPE on the regulation of RANKL-induced osteoclastogenesis, bone resorption and signaling pathways. Low concentrations of CAPE (<1 microM) dose dependently inhibited RANKL-induced osteoclastogenesis in RAW264.7 cell and bone marrow macrophage (BMM) cultures, as well as decreasing the capacity of human osteoclasts to resorb bone. CAPE inhibited both constitutive and RANKL-induced NF-kappaB and NFAT activation, concomitant with delayed IkappaBalpha degradation and inhibition of p65 nuclear translocation. At higher concentrations, CAPE induced apoptosis and caspase 3 activities of RAW264.7 and disrupts the microtubule network in osteoclast like (OCL) cells. Taken together, our findings demonstrate that inhibition of NF-kappaB and NFAT activation by CAPE results in the attenuation of osteoclastogenesis and bone resorption, implying that CAPE is a potential treatment for osteolytic bone diseases.
核因子κB受体活化因子配体（RANKL）激活的信号传导对于破骨细胞的分化、激活和存活至关重要。咖啡酸苯乙酯（CAPE）是一种来自蜜蜂蜂胶的天然核因子κB抑制剂，已被证明具有抗肿瘤和抗炎特性。在本研究中，我们研究了CAPE对RANKL诱导的破骨细胞生成、骨吸收和信号通路调节的影响。低浓度的CAPE（<1 microM）剂量依赖性地抑制RAW264.7细胞和骨髓巨噬细胞（BMM）培养物中RANKL诱导的破骨细胞生成，同时降低人破骨细胞的骨吸收能力。CAPE抑制组成型和RANKL诱导的核因子κB和活化T细胞核因子（NFAT）激活，同时延迟IκBα降解并抑制p65核转位。在较高浓度下，CAPE诱导RAW264.7细胞凋亡和半胱天冬酶3活性，并破坏破骨样（OCL）细胞中的微管网络。综上所述，我们的研究结果表明，CAPE对核因子κB和NFAT激活的抑制导致破骨细胞生成和骨吸收减弱，这意味着CAPE是溶骨性骨疾病的一种潜在治疗方法。
