Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL‐induced osteoclastogenesis

Jin, Haiming; Wang, Qingqing; Chen, Kai; Xu, Ke; Pan, Hao; Chu, Feifan; Ye, Zhen; Wang, Ziyi; Tickner, Jennifer; Qiu, Heng; Wang, Chao; Kenny, Jacob; Xu, Huazi; Wang, Te; Xu, Jiake

doi:10.1111/jcmm.14713

Cited by 19 publications

(12 citation statements)

References 52 publications

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“…Bisphosphonates and denosumab have been shown to give rise to osteonecrosis of the jaw ( Hamadeh et al, 2015 ; Khan et al, 2015 ; Boquete-Castro et al, 2016 ), and teriparatide can increase the risk of osteosarcoma ( Gilsenan et al, 2018 ). Compared with synthetic chemicals, natural compounds seem to have an advantage in terms of safety, some of which inhibit bone resorption and bone loss in OVX mice ( Jin et al, 2019 ; Zhou et al, 2019 ; Zhou et al, 2020 ). In this study, we explored the therapeutic effects of NOT on osteoclasts and OVX-mediated bone loss.…”

Section: Discussionmentioning

confidence: 99%

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species

Chen

Wang

et al. 2021

Front. Pharmacol.

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Integrity of the skeleton is sustained through the balanced activities of osteoblasts and osteoclasts in bone remodeling unit. The balance can be disrupted by excessive osteoclasts activation commonly seen in osteoporosis. Notopterol (NOT) is a main component of Notopterygium incisum which exerts a wide spectrum effect on biomedical pharmacology. In our study, we found NOT serves as an inhibitor in regulating RANKL-activated osteoclasts formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays. Furthermore, RANKL-mediated signaling pathways including MAPK, NF-κB and calcium ossification were hampered, whereas ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathways were promoted by NOT. In addition, the activation of the essential transcription factor NFATc1 in RANKL-mediated osteoclastogenesis was almost totally suppressed by NOT. What is more, NOT diminished the loss of bone mass in preclinical model of OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining. Conclusively, our findings demonstrated that NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways in vitro, and prohibit bone loss induced by OVX in vivo. Taken together, NOT may be identified to be a natural and novel treatment for osteolytic diseases.

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Section: Discussionmentioning

confidence: 99%

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species

Chen

Wang

et al. 2021

Front. Pharmacol.

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“…Natural compounds with a broad spectrum of biological activity and limited side-effects have become the main targets of our research. There have been many studies on the treatment of osteoporosis using natural compounds (7)(8)(9) that have provided us with a reliable theoretical and technological basis for our exploration into the field.…”

Section: Introductionmentioning

confidence: 99%

Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways

Zhu

Jiang

et al. 2021

Front. Endocrinol.

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Osteoclasts (OCs) play an important role in osteoporosis, a disease that is mainly characterized by bone loss. In our research, we aimed to identify novel approach for regulating osteoclastogenesis and thereby treating osteoporosis. Previous studies have set a precedent for screening traditional Chinese herbal extracts for effective inhibitors. Peiminine is an alkaloid extracted from the bulb of Fritillaria thunbergii Miq that reportedly has anticancer and anti-inflammatory effects. Thus, the potential inhibitory effect of peiminine on OC differentiation was investigated via a series of experiments. According to the results, peiminine downregulated the levels of specific genes and proteins in vitro and consequently suppressed OC differentiation and function. Based on these findings, we further investigated the underlying molecular mechanisms and identified the NF-κB and ERK1/2 signaling pathways as potential targets of peiminine. In vivo, peiminine alleviated bone loss in an ovariectomized mouse model.

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“…Although these drugs showed inhibitory effect on osteoclast activity, they had no effect on osteogenic activity. [14][15][16] Simply reducing osteoclast activity may interfere with bone formation, reduce bone transformation and bring side effects such as mandibular osteonecrosis. Studies have shown that the proliferation of early osteoclasts requires the activation of β-catenin; however, the activated β-catenin inhibits the differentiation of osteoclasts.…”

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confidence: 99%

Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

Yan

Tang

Chen

et al. 2019

J Cellular Molecular Medi

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Osteoporosis is caused by disturbance in the dynamic balance of bone remodelling, a physiological process, vital for maintenance of healthy bone tissue in adult humans. In this process, a new bone is formed by osteoblasts and the pre‐existing bone matrix is resorbed by osteoclasts. Imperatorin, a widely available and inexpensive plant extract with antioxidative and apoptotic effects, is reported to treat osteoporosis. However, the underlying mechanism and specific effects on bone metabolism have not been elucidated. In this study, we used rat bone marrow‐derived mesenchymal stem cells and found that imperatorin can activate RUNX2, COL1A1 and osteocalcin by promoting the Ser9 phosphorylation of GSK3β and entry of β‐catenin into the nucleus. Imperatorin also enhanced the production of phospho‐AKT (Ser473), an upstream factor that promotes the Ser9 phosphorylation of GSK3β. We used ipatasertib, a pan‐AKT inhibitor, to inhibit the osteogenic effect of imperatorin, and found that imperatorin promotes osteogenesis via AKT/GSK3β/β‐catenin pathway. Next, we used rat bone marrow‐derived monocytes, to check whether imperatorin inhibits osteoclast differentiation via AKT/GSK3β/β‐catenin pathway. Further, we removed the bilateral ovaries of rats to establish an osteoporotic model. Intragastric administration of imperatorin promoted osteogenesis and inhibited osteoclast in vivo. Our experiments showed that imperatorin is a potential drug for osteoporosis treatment.

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Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL‐induced osteoclastogenesis

Cited by 19 publications

References 52 publications

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis via Repressing RANKL Signaling and Reactive Oxygen Species

Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways

Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

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