Zhang Wenhao, Zhang Weijie, Huo Liang, Chai Ying, Liu Zhiyang, Ren Zhenhu, Yu Chuangqi
Department of Oral and Craniofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Oral and Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ann Transl Med. 2021 Mar;9(5):383. doi: 10.21037/atm-20-4255.
Bone homeostasis is mediated by osteoblast-related bone formation and osteoclast-related resorption. The imbalance of bone homeostasis due to excessive osteoclastogenesis or reduced osteogenesis can result in various disorders, such as postmenopausal osteoporosis (PMOP). The receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways are essential in osteoclastogenesis. In this study, we aimed to investigate the effects of rosavin, an alkylbenzene diglycoside compound from the traditional Chinese medicine Rhodiola Rosea L, on RANKL-induced osteoclastogenesis and .
The effects of rosavin on osteoclastogenesis were assessed by TRAP staining of bone marrow monocyte cells (BMMCs) and RAW 264.7 cells. The effects of rosavin on osteogenesis were determined using alkaline phosphatase (ALP) and alizarin red staining, as well as real-time quantitative reverse transcription polymerase chain reaction. Actin ring formation and bone formation experiments were performed to evaluate osteoclast function. Western blotting was carried out to determine the expression of osteoclastogenesis-related genes, and the activation of the NF-κB and MAPK pathways was evaluated by performing western blotting and immunofluorescence staining. Ovariectomized mice were used to explore the effect of rosavin on bone loss.
Rosavin could inhibit osteoclastogenesis, suppress the function of osteoclasts, and decrease the expression of osteoclast differentiation-related genes, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, matrix metalloproteinase-9 (MMP-9), calcitonin receptor (CTR), TNF receptor-associated factor 6 (TRAF-6), receptor activator of nuclear factor-κB (RANK), and colony-stimulating factor-1 receptor (c-fms). Rosavin inhibited RANKL-induced phosphorylation of p65 and inhibitory subunit of NF-κB alpha (IκBα), and suppressed p65 nuclear translocation. Rosavin was also found to inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Furthermore, rosavin promoted osteogenesis in bone marrow mesenchymal stem cells (BMSCs). experiments showed that treatment with rosavin could alleviate ovariectomy-induced osteoporosis in mice.
Our results indicated that rosavin suppressed RANKL-induced osteoclastogenesis and by blocking the NF-κB and MAPK pathways. Rosavin treatment is a potential therapy for the clinical treatment of osteoclastogenesis-related disorders.
骨稳态由成骨细胞相关的骨形成和破骨细胞相关的骨吸收介导。由于破骨细胞生成过多或成骨减少导致的骨稳态失衡可引发多种疾病，如绝经后骨质疏松症（PMOP）。核因子κB受体活化剂配体（RANKL）诱导的活化B细胞核因子κB轻链增强子（NF-κB）和丝裂原活化蛋白激酶（MAPK）通路在破骨细胞生成中至关重要。在本研究中，我们旨在探讨红景天苷（一种来自中药红景天的烷基苯二糖苷化合物）对RANKL诱导的破骨细胞生成的影响。
通过对骨髓单核细胞（BMMCs）和RAW 264.7细胞进行抗酒石酸酸性磷酸酶（TRAP）染色来评估红景天苷对破骨细胞生成的影响。使用碱性磷酸酶（ALP）和茜素红染色以及实时定量逆转录聚合酶链反应来确定红景天苷对成骨的影响。进行肌动蛋白环形成和骨形成实验以评估破骨细胞功能。通过蛋白质免疫印迹法测定破骨细胞生成相关基因的表达，并通过蛋白质免疫印迹法和免疫荧光染色评估NF-κB和MAPK通路的激活情况。使用去卵巢小鼠来探究红景天苷对骨质流失的影响。
红景天苷可抑制破骨细胞生成，抑制破骨细胞功能，并降低破骨细胞分化相关基因的表达，包括抗酒石酸酸性磷酸酶（TRAP）、组织蛋白酶K、基质金属蛋白酶-9（MMP-9）、降钙素受体（CTR）、肿瘤坏死因子受体相关因子6（TRAF-6）、核因子κB受体活化剂（RANK）和集落刺激因子-1受体（c-fms）。红景天苷抑制RANKL诱导的p65和NF-κBα抑制亚基（IκBα）的磷酸化，并抑制p65核转位。还发现红景天苷可抑制细胞外信号调节激酶（ERK）、p38和c-Jun氨基末端激酶（JNK）的磷酸化。此外，红景天苷促进骨髓间充质干细胞（BMSCs）的成骨作用。实验表明，红景天苷治疗可减轻去卵巢诱导的小鼠骨质疏松症。
我们的结果表明，红景天苷通过阻断NF-κB和MAPK通路抑制RANKL诱导的破骨细胞生成。红景天苷治疗是一种用于临床治疗破骨细胞生成相关疾病的潜在疗法。
