Acacetin inhibits RANKL-induced osteoclastogenesis and LPS-induced bone loss by modulating NFATc1 transcription

Jin, Ming; Nie, Jiangbo; Zhu, Juli; Li, Jing; Fang, Tianshun; Xu, Juntao; Jiang, Xuesheng; Chen, Zhuo; Li, Jianyou; Wu, Fengfeng

doi:10.1016/j.bbrc.2021.10.066

Cited by 9 publications

(6 citation statements)

References 29 publications

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“…LPS treatment can activate the immune cells, which in turn stimulates the inflammatory response and produces cytokines that increase the recruitment and activity of osteoclast, leading to bone loss [ 24 ]. It has been reported that injection of LPS for twice to mice within 10 days can cause acute inflammatory response and the activation of osteoclast and bone destruction [ 16 ]. Therefore, injection of LPS is currently one of the most recognized animal models for studying inflammatory bone loss [ 19 , 25 ] and has been widely applied in lots of investigation with the aim to observe the effects of drugs on inflammatory bone loss [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Forty healthy C57/BL6 mice were equally randomized to four groups: PBS control group, 5 mg/kg LPS treatment group, combination treatment group using 5 mg/kg LPS and 40 mg/kg Mon, and combination treatment group using 5 mg/kg LPS and 80 mg/kg Mon. Mice were injected intraperitoneally with LPS or the same volume of PBS on day 2 and 6, and Mon was given at day 1, 3, 5, 7 and 9 [ 16 ]. At day 10, the mice were fasted for 12 h, and urine was collected from each mouse.…”

Section: Methodsmentioning

confidence: 99%

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Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3β Pathway

Zhang

Song

et al. 2022

Nutrients

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Monotropein (Mon) is a kind of iridoid glycoside plant secondary metabolite primarily present in some edible and medicinal plants. The aim of this study was to investigate the effect of Mon on lipopolysaccharide (LPS)-induced inflammatory bone loss in mice and osteoclasts (OCs) derived from bone marrow-derived macrophages (BMMs), and explore the mechanisms underlying the effect of Mon on LPS-induced osteoclastogenesis. It was found that Mon markedly attenuated deterioration of the bone micro-architecture, enhanced tissue mineral content (TMC) and bone volume/total volume (BV/TV), reduced structure model index (SMI) and trabecular separation/spacing (Tb.Sp) in the bone tissue and decreased the activities of tartrate resistant acid phosphatase-5b (TRACP-5b), receptor activator NF-κB (RANK), and receptor activator NF-κB ligand (RANKL) as well as the serum levels of interleukin 6 (IL-6) and interleukin 1β (IL-1β) in LPS-treated mice. In addition, Mon treatment reduced the number of TRAP positive OCs in the bone tissue of LPS-treated mice and also exerted a stronger inhibitory effect on formation, differentiation, and F-actin ring construction of OCs derived from BMMs. Mon significantly inhibited the expression of the nuclear factor of activated T-cells c1 (NFATc1) and the immediate early gene (C-Fos) and nuclear translocation of NFATc1 in LPS-treated OCs, thereby inhibiting the expression of matrix metalloproteinase-9 (MMP-9), cathepsin K (CtsK), and TRAP. Mon significantly inhibited the expression of TRAF6, phosphorylation of P65, and degradation of IKBα, thus inhibiting the activation of NF-κB pathway in LPS-induced inflammatory mice and OCs derived from BMMs, and also inhibited LPS-induced phosphorylation of protein kinase B (Akt) and Glycogen synthase kinase 3β (GSK-3β) in OCs derived from BMMs. In conclusion, these results suggested that Mon could effectively inhibit osteoclastogenesis both in vitro and in vivo and therefore may prove to be potential option for prevention and treatment of osteoclastic bone resorption-related diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3β Pathway

Zhang

Song

et al. 2022

Nutrients

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“…The three‐dimensional visualization was accomplished after the samples had been placed in the sample tank and the scanning settings had been set. The microstructure and parameters in the lesion area of mice, including the trabecular number (Tb.N), bone volume (BV/TV), structural mode index (SMI), trabecular thickness (Tb.Th), trabecular connection density (Conn.D), and trabecular separation (Tb.Sp), were measured and analyzed (Jin et al, 2021 ; Lee et al, 2021 ; Wang, Ding, et al, 2021 ; Wang, Wang, et al, 2021 ; Yang et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Sika deer velvet antler protein extract modulater bone metabolism and the structure of gut microbiota in ovariectomized mice

Wang

et al. 2023

Food Science & Nutrition

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Osteoporosis is a systemic osteopathy characterized by bone metabolism disorders that become more serious with age increases in postmenopausal women. Recent studies have found that antler protein is the main bioactive component of cervus pantotrichum, and it has a positive regulatory effect on bone metabolism and can improve estrogen level. This study aimed to investigate the effect of velvet antler extract (VAE) on the prevention of osteoporosis and the modulation of gut microbiota in ovariectomized (OVX) mice. OVX mice treated with 12 weeks of VAE exhibited higher levels of serum BGP, Ca2+, CT, and HyP (p < .05). Micro‐CT scans showed that VAE significantly elevated bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone connection density (Conn.D), decreased trabecular separation (Tb.Sp), and structural modality index (SMI) than untreated OVX mice. The right tibial retinaculum in the VAE group was clearer, with a clearer reticular structure, smaller gaps, a tighter distribution, and a more orderly arrangement. The gut microbiota of the cecal contents was analyzed by 16 s rDNA amplicon sequencing. The data indicated that VAE modulated the species, numbers, and diversity of the gut microbiota in OVX mice. Ovariectomy caused dysbiosis of the intestinal microbiota by increasing the ratio of Firmicutes to Bacteroidetes in mice, but the ratio decreased after treatment with VAE. These results suggest that VAE has a therapeutic effect on OVX mice via modulate bone‐related biochemical markers in serum and structure of gut microbiota.

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“…Acacetin is a flavonoid compound from Saussurea involucrata plant and Damiana . Acacetin has been found to have anti-inflammatory ( Ren et al, 2020 ; Singh et al, 2020 ), antioxidant ( Song et al, 2022 ; Wu et al, 2022 ), anti-cancer ( Wang S. et al, 2020 ; Yun et al, 2021 ), anti-osteoporosis ( Jin et al, 2021 ; Lin et al, 2022 ), anti-diabetic ( Han et al, 2020 ; Song et al, 2022 ) and other properties. Acacetin reportedly inhibits TBHP-induced ROS production by upregulating the expression of antioxidant proteins such as HO1, NQO1, and SOD in NP cells ( Wang H. et al, 2020 ).…”

Section: Phytochemicals For the Treatment Of Idd By Targeting Inflamm...mentioning

confidence: 99%

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

et al. 2022

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Low back pain is a major cause of disability worldwide that declines the quality of life; it poses a substantial economic burden for the patient and society. Intervertebral disc (IVD) degeneration (IDD) is the main cause of low back pain, and it is also the pathological basis of several spinal degenerative diseases, such as intervertebral disc herniation and spinal stenosis. The current clinical drug treatment of IDD focuses on the symptoms and not their pathogenesis, which results in frequent recurrence and gradual aggravation. Moreover, the side effects associated with the long-term use of these drugs further limit their use. The pathological mechanism of IDD is complex, and oxidative stress and inflammation play an important role in promoting IDD. They induce the destruction of the extracellular matrix in IVD and reduce the number of living cells and functional cells, thereby destroying the function of IVD and promoting the occurrence and development of IDD. Phytochemicals from fruits, vegetables, grains, and other herbs play a protective role in the treatment of IDD as they have anti-inflammatory and antioxidant properties. This article reviews the protective effects of phytochemicals on IDD and their regulatory effects on different molecular pathways related to the pathogenesis of IDD. Moreover, the therapeutic limitations and future prospects of IDD treatment have also been reviewed. Phytochemicals are promising candidates for further development and research on IDD treatment.

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Acacetin inhibits RANKL-induced osteoclastogenesis and LPS-induced bone loss by modulating NFATc1 transcription

Cited by 9 publications

References 29 publications

Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3β Pathway

Monotropein Protects against Inflammatory Bone Loss and Suppresses Osteoclast Formation and Bone Resorption by Inhibiting NFATc1 via NF-κB and Akt/GSK-3β Pathway

Sika deer velvet antler protein extract modulater bone metabolism and the structure of gut microbiota in ovariectomized mice

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

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