C-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-κB activation
C-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-κB activation
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DOI：
10.1038/s41598-020-59363-y
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发表时间：
2020-02-13
影响因子：
4.6
通讯作者：
Chellaiah, Meenakshi A.
中科院分区：
文献类型：
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作者：
AlQranei, Mohammed S.;Aljohani, Hanan;Chellaiah, Meenakshi A.
炎症性疾病如牙周炎和骨质疏松症会导致骨丢失过多。其机制与巨噬细胞分化为多核巨破骨细胞及其骨吸收活性有关。藻蓝蛋白（C-Phycocyanin，C-PC）是从蓝藻中提取的一种藻胆蛋白，具有多种药理作用。C-PC在骨代谢中的作用有待进一步揭示。在这项研究中，我们确定了C-PC作为体外破骨细胞分化，活性和存活抑制剂的有效性。我们发现，C-PC强烈抑制巨噬细胞分化成TRAP阳性破骨细胞，独特的破骨细胞特异性足状体组织，和牙本质基质吸收没有任何细胞毒性。此外，它抑制破骨细胞特异性标志物的表达，如组织蛋白酶K和整合素β 3在mRNA和蛋白质水平。RANKL介导的信号传导利用活性氧（ROS）来分化破骨细胞。C-PC减弱RANKL刺激的ROS。机制研究表明，C-PC具有通过阻断胞质I κ B-α的降解从而活化下游标志物如c-Fos和NFATc 1来减少破骨细胞形成的潜力。然而，它在体外对成骨细胞介导的骨形成没有任何影响。总的来说，我们的数据表明，C-PC可以用作治疗剂，可以靶向骨吸收过度骨细胞介导的骨丢失，而不影响骨中的成骨细胞活性。
Excessive bone loss occurs in inflammatory disorders such as periodontitis and osteoporosis. The underlying mechanism is related to the differentiation of macrophages into multinucleated giant osteoclasts and their bone resorptive activity. C-Phycocyanin (C-PC) is a phycobiliprotein extracted from the blue-green algae, which has been shown to have various pharmacological effects. The role of C-PC on bone metabolism needs revelation. In this study, we determined the effectiveness of C-PC as an inhibitor of osteoclast differentiation, activity, and survival in vitro. We found that C-PC strongly inhibited the differentiation of macrophages to TRAP-positive osteoclasts, distinctive osteoclast specific podosomal organization, and dentine matrix resorption without any cytotoxicity. Also, it suppressed the expression of osteoclast specific markers, such as cathepsin K and integrin beta 3 at mRNA and protein levels. RANKL mediated signaling utilizes reactive oxygen species (ROS) for the differentiation of osteoclasts. C-PC attenuated RANKL stimulated ROS. Mechanistic studies indicate that C-PC has the potential to reduce osteoclast formation via blocking the degradation of cytosolic I kappa B-alpha and hence, the activation of downstream markers such as c-Fos and NFATc1. However, it does not have any effect on osteoblast-mediated bone formation in vitro. Collectively, our data suggest that C-PC may be utilized as a therapeutic agent that can target bone loss mediated by excessive osteoclastic bone resorption without affecting osteoblastic activity in bone.