Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL‐induced osteoclastogenesis

Chen, Xiao; Zhi, Xiao; Pan, Panpan; Cui, Jin; Cao, Liehu; Weng, Weizong; Zhou, Qirong; Wang, Lin; Zhai, Xiao; Zhao, Qingiie; Hu, Honggang; Huang, Biaotong; Su, Jiacan

doi:10.1096/fj.201700316r

Cited by 79 publications

(77 citation statements)

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“…Activation of the MAPK and the AKT pathway play significantly in osteoclast formation (Chen et al, ; Deepak, Kasonga, Kruger, & Coetzee, ). Therefore, to determine the effects of THF on MAPK and AKT following the stimulation of RANKL in RAW 264.7 and BMM cells, we investigated the phosphorylation of ERK, JNK, p38, and AKT by western blot assay.…”

Section: Resultsmentioning

confidence: 99%

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6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

Kim

Lee

et al. 2019

Phytotherapy Research

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The balance between the osteoblasts and the osteoclasts is important for the maintenance of the skeleton of the human body. The osteoclasts absorb bone after differentiated into polymorphonuclear cells by the fusion of monocytes/macrophages. We have found that 6,7,4′‐Trihydroxyflavone (THF), a compound from the heartwood of Dalbergia Odorifera inhibits receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation, actin ring formation, and bone resorption in RAW 264.7 cells and bone marrow macrophage. THF significantly inhibited the c‐Jun‐N‐terminal kinase signaling pathway without affecting extracellular signal‐regulated kinase, p38, and AKT signaling. Moreover, THF inhibited the expression of c‐Fos, nuclear factor‐activated T cells cytoplasm 1, cathepsin K, and c‐src by RANKL. We used a lipopolysaccharide (LPS)‐induced bone loss model in mice. Consequently, bone volume per tissue volume, trabecular number's reduction was recovered in THF‐treated mice, and trabecular separation's augmentation was also attenuated by THF administration. In summary, THF inhibits RANKL‐induced osteoclast differentiation by MAPK signaling pathway and inhibits bone resorption by destroying the actin ring in mature osteoclasts. THF also prevented LPS‐induced bone loss in a mice model. Thus, THF may be useful in the treatment of bone diseases associated with excessive osteoclast differentiation and bone resorption.

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Section: Resultsmentioning

confidence: 99%

“…RANKL‐induced NF‐kB activation is known to be essential for osteoclast differentiation and function (Chen et al, ). NF‐κB was activated by RANKL through phosphorylation of IKK and subsequent phosphorylated and degradation of IκBα (Deepak et al, ).…”

Section: Resultsmentioning

confidence: 99%

6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

Kim

Lee

et al. 2019

Phytotherapy Research

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“…Nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) is the central transcriptional factor in osteoclastogenesis and is responsible for the transcription of osteoclast-related genes, including matrix metalloproteinase (MMP)-9, cathepsin K, latent transforming growth factor beta binding protein 3, tartrate-resistant acid phosphatase (TRAP), and c-Src [4]. Finally, intracellular Ca 2+ is released, and NFATc1 is activated and osteoclastogenesis is promoted [5]. Previous studies demonstrated that overactive osteoclast function could also be induced by a deficiency of estrogen accompanied by increased levels of proinflammatory cytokines and RANKL after menopause [6,7].…”

Section: Introductionmentioning

confidence: 99%

Shikimic Acid Inhibits Osteoclastogenesis in Vivo and in Vitro by Blocking RANK/TRAF6 Association and Suppressing NF-κB and MAPK Signaling Pathways

Chen

Zhai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Bone homeostasis is associated with the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Unbalanced bone homeostasis as a result of reduced osteogenesis or excessive osteoclastogenesis can lead to disorders such as osteoporosis, Paget’s disease, and rheumatoid arthritis. Shikimic acid is a cyclohexanecarboxylic acid, reported to exhibit pharmacological properties including anti-inflammatory and antioxidant activities. However, its effects on bone homeostasis remain unknown. Methods: First, the in vitro MTT cell viability assay was performed. Tartrate-resistant acid phosphatase (TRAP) and actin ring formation assays, as well as immunofluorescence staining were then performed to evaluate osteoclastogenesis. Potential signaling pathways were characterized by western blotting and verified in overexpression experiments. Related factors were examined by western blotting, reverse transcription polymerase chain reaction, electrophoretic mobility shift assay, and co-immunoprecipitation. Ovariectomized mice were used for the in vivo study. Results: TRAP staining showed that shikimic acid significantly inhibited osteoclastogenesis and pit resorption in bone marrow monocytes and RAW264.7 cells, and actin ring formation assays showed that shikimic acid suppressed the bone resorption function of osteoclasts. Furthermore, shikimic acid inhibited the receptor activator of nuclear factor-κB RANK/tumor necrosis factor receptor-associated factor 6 (TRAF6) association, suppressed nuclear factor-κB and mitogen-activated protein kinase signaling pathways, and downregulated nuclear factor of activated T-cell cytoplasmic 1. The expression of osteoclastogenesis biomarkers, including TRAF6, calcitonin receptor, TRAP, cathepsin K, and matrix metalloproteinase-9, was inhibited. In vivo, shikimic acid also significantly ameliorated bone loss and prevented osteoclastogenesis in ovariectomized mice. Conclusion: Shikimic acid inhibited osteoclastogenesis and osteoclast function by blocking RANK ligand-induced recruitment of TRAF6, as well as downstream signaling pathways in vitro. Shikimic acid also reduced ovariectomy-induced osteoclastogenesis and bone loss in vivo.

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“…At the same time, the involvement of EPCs in the early bone resorption activity is an important event for promoting skeletal development [8, 14]. OCs are specialized multinucleated cells derived from hematopoietic stem cells or monocytes/macrophage progenitor cells [15]. There are three different stages during osteoclastogenesis: preosteoclast (Pre-OC), newborn osteoclast (N-OC) and mature osteoclast (M-OC) [16-18].…”

Section: Introductionmentioning

confidence: 99%

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells

Quan

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the process of bone development and remodeling, the vasculature is regarded as the communicative network between the bone and neighboring tissues. Recently, it has been reported that the processes of angiogenesis and osteogenesis are coupled temporally and spatially. However, few studies reported the relationship and relevant mechanism between osteoclastogenesis and vasculogenesis. Methods: Arraystar Mouse lncRNA microarray V3.0 was firstly used to analyze the differentially expressed lncRNA genes in osteoclast different stages during osteoclastogenesis. Cell counting kit 8 (CCK-8) analysis, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, migration and tube formation assays were used to detect impact of osteoclast different stages on the proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs), respectively. Finally, transfection of AK131850 shRNA, miR-93-5p mimic and miR-93-5p inhibitor, qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA), fluorescence in situ hybridization (FISH) and luciferase reporter assay were carried out to dissect molecular mechanisms. Results: In this study, we found that newborn OCs (N-OC) and mature OCs (M-OC) during osteoclastogenesis significantly promoted proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs). Through lncRNA microarray and GO&pathway analysis, we found that AK131850 and co-expressed gene, vascular endothelial growth factor a (VEGFa), were significantly up-regulated in N-OC and M-OC. After inhibition of AK131850 the promoting effect of N-OC and M-OC on EPCs was reversed. Furthermore, we found that AK131850 directly competed miR-93-5p in N-OC and M-OC through sponge, thereby increasing VEGFa transcription, expression and secretion through derepressing of miR-93-5p on VEGFa. Conclusion: Our results provided the first finding that lncRNA-AK131850 sponged miR-93-5p in N-OC and M-OC during osteoclastogenesis to enhance the secretion of VEGFa, thus promoting vasculogenesis of EPCs.

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Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL‐induced osteoclastogenesis

Cited by 79 publications

References 50 publications

6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

Shikimic Acid Inhibits Osteoclastogenesis in Vivo and in Vitro by Blocking RANK/TRAF6 Association and Suppressing NF-κB and MAPK Signaling Pathways

LncRNA-AK131850 Sponges MiR-93-5p in Newborn and Mature Osteoclasts to Enhance the Secretion of Vascular Endothelial Growth Factor a Promoting Vasculogenesis of Endothelial Progenitor Cells

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