Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway

Zhao, Shuai; Sun, Yu; Li, Xiaolei; Wang, Jingcheng; Yan, Lianqi; Zhang, Zhen; Wang, Daxin; Dai, Jihang; He, Jun; Wang, Shuguang

doi:10.1016/j.intimp.2016.09.031

Cited by 26 publications

(39 citation statements)

References 28 publications

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“…Taxifolin, a flavonol with strong anti-oxidative effect, has been proven to promote osteogenic differentiation of human BMSCs in our previous research [22]. It has been proved that several other flavonoids and active components isolated from Chinese herb, such as scutellarin [23], schisantherin [24], tenuigenin [25], and gastrodin [26], inhibit osteoclast formation via RANKL or NFATc1 signaling pathways. In this investigation, the suppression effects of taxifolin on the RANKLinduced osteoclastogenesis of human BMMs as well as the protection effects in LPS-induced bone lysis mouse model have been demonstrated.…”

Section: Discussionmentioning

confidence: 94%

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

et al. 2018

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It has been reported that taxifolin inhibit osteoclastogenesis in RAW264.7 cells. In our research, the inhibition effects of taxifolin on the osteoclastogenesis of human bone marrow-derived macrophages (BMMs) induced by receptor activator of NF-κB ligand (RANKL) as well as the protection effects in lipopolysaccharide-induced bone lysis mouse model have been demonstrated. In vitro, taxifolin inhibited RANKL-induced osteoclast differentiation of human BMMs without cytotoxicity. Moreover, taxifolin significantly suppressed RANKL-induced gene expression, including tartrate-resistant acid phosphatase, matrix metalloproteinase-9 nuclear factor of activated T cells 1 and cathepsin K, and F-actin ring formation. Further studies showed that taxifolin inhibit osteoclastogenesis via the suppression of the NF-κB signaling pathway. In vivo, taxifolin prevented bone loss in mouse calvarial osteolysis model. In conclusion, the results suggested that taxifolin has a therapeutic potential for osteoclastogenesis-related diseases such as osteoporosis, osteolysis, and rheumatoid arthritis.

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Section: Discussionmentioning

confidence: 94%

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

et al. 2018

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“…Till date, many natural extracts have gained ground in the management of periprosthetic osteolysis (Xiao et al, 2015;Zhao et al, 2016;Meng et al, 2018) due to identical biological safety testified in the longevity of traditional Chinese medicine and affordable prices. T. farfara is one of the most commonly used herbal medicines in East Asian and European traditional medicine for treating cough or asthma.…”

Section: Discussionmentioning

confidence: 99%

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways

Yin

Chen

et al. 2020

Front. Pharmacol.

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Background: Aseptic prosthetic loosening is one of the main factors causing poor prognosis of limb function after joint replacement and requires troublesome revisional surgery. It is featured by wear particle-induced periprosthetic osteolysis mediated by excessive osteoclasts activated in inflammatory cell context. Some natural compounds show antiosteoclast traits with high cost-efficiency and few side effects. Tussilagone (TUS), which is the main functional extract from Tussilago farfara generally used for relieving cough, asthma, and eliminating phlegm in traditional medicine has been proven to appease several RAW264.7-mediated inflammatory diseases via suppressing osteoclast-related signaling cascades. However, whether and how TUS can improve aseptic prosthetic loosening via modulating osteoclast-mediated bone resorption still needs to be answered. Methods:We established a murine calvarial osteolysis model to detect the preventative effect of TUS on osteolysis in vivo. Micro-CT scanning and histomorphometric analysis were used to determine the variation of bone resorption and osteoclastogenesis. The antiosteoclast-differentiation and anti-bone-resorption bioactivities of TUS in vitro were investigated using bone slice resorption pit evaluation, and interference caused by cytotoxicity of TUS was excluded according to the CCK-8 assay results. Quantitative polymerase chain reaction (qPCR) analysis was applied to prove the decreased expression of osteoclast-specific genes after TUS treatment. The inhibitory effect of TUS on NF-kB and p38 MAPK signaling pathways was testified by Western blot and NF-kB-linked luciferase reporter gene assay.Results: TUS better protected bones against osteolysis in murine calvarial osteolysis model with reduced osteoclasts than those in the control group. In vitro studies also showed that TUS exerted antiosteoclastogenesis and anti-bone-resorption effects in both bone marrow macrophages (BMMs) and RAW264.7 cells, as evidenced by the decline of Frontiers in Pharmacology | www.frontiersin.org osteoclast-specific genes according to qPCR. Western blotting revealed that TUS treatment inhibited IkBa degradation and p38 phosphorylation. Conclusions:Collectively, our studies proved for the first time that TUS inhibits osteoclastogenesis by suppressing the NF-kB and p38 MAPK signaling pathways, therefore serving as a potential natural compound to treat periprosthetic osteolysisinduced aseptic prosthetic loosening.

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“…A-C, BMMs were stimulated with M-CSF, RANKL, and 0, 1.25, 2.5 or 5 μM Arc. 8,9 In normal cells, NF-κB is retained in the cytoplasm through combining with the inhibitory IκB protein. D and E, BMMs were seeded onto hydroxyapatite-coated plate and treated with the indicated concentrations of Arc.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Generally, wear particle stimulates recruitment of macrophages, fibroblasts, osteoblasts, and osteoclasts, and stimulates these cells to produce and secrete various cytokines and chemokines. 8,9 Therefore, the NF-κB signaling pathway is very important to stimulate periprosthetic osteolysis. 7 Considering the importance of osteoclast in this osteolytic disease, therapeutic targeting of excessive osteoclast formation provides a logical method for the treatment or prevention of wear particle-induced osteolysis and pathological bone loss.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 These factors can, directly and indirectly, initiate overexpression of receptor activator of nuclear factor κΒ ligand (RANKL) and suppression of osteoprotegerin in osteoblasts, and subsequently induce excessive osteoclast formation and bone resorption. 8,9 Actually, several agents targeting osteoclast differentiation have been studied over the last decade, including bisphosphonates, erythromycin, strontium ranelate, and denosumab (a RANKL inhibitor). Osteoclasts are multinucleated giant cells originated from monocytes/macrophage progenitors through differentiation process mainly regulated by two key factors, including RANKL and macrophage colony-stimulating factor (M-CSF).…”

Section: Introductionmentioning

confidence: 99%

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Arctigenin inhibits RANKL‐induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle–induced bone loss in vivo

Wei

Liang

Wei

et al. 2018

J of Cellular Biochemistry

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Wear particle–induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle–induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle–induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti‐inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle–induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle–induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow–derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast‐related signaling pathways. The results showed that arctigenin inhibited RANKL‐induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose‐dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF‐κB) ligand–induced NF‐κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast‐related osteolytic diseases caused by excessive osteoclast formation.

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Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway

Cited by 26 publications

References 28 publications

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways

Arctigenin inhibits RANKL‐induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle–induced bone loss in vivo

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