Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast

Hong, Seong Ahn; Lee, Jiae; Seo, Dong Han; Lee, Hyein; Park, Doo Ri; Lee, Gong Rak; Jo, You Jin; Kim, Na-Rae; Kwon, Min‐Jung; Shon, Hansem; Seo, Eun Kyoung; Kim, Han Sung; Lee, Soo Young; Jeong, Woojin

doi:10.1016/j.freeradbiomed.2017.07.030

Cited by 34 publications

(36 citation statements)

References 54 publications

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“…Recombinant human MCSF and mouse RANKL proteins were prepared as previously described (47). SFII was purchased from ChemFaces (Wuhan, China), and LPS was purchased from MilliporeSigma (Burlington, MA, USA).…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

“…The cDNA was amplified in a reaction mixture containing SYBR Green PCR Master Mix (Bioline, Taunton, MA, USA) and 1 mM genespecific primer using an ABI 7300 real-time PCR System (Applied Biosystems, Foster City, CA, USA). The sequences of the primers used in the current study other than those used in previous report (47) are shown in Supplemental Table S1. The amplification protocol consisted of an initial step of 2 min at 50°C and 2 min at 95°C followed by 40 cycles of 15 s at 95°C and 1 min at 60°C.…”

Section: Rna Isolation Reverse Transcription and Real-time Pcr Analmentioning

confidence: 99%

“…The intracellular ROS were assayed as previously described (23,47). Briefly, at various time points after incubation with RANKL, the cells were washed with HBSS and incubated with 5 mM 5-(and-6-)chloromethyl-29,79-dichlorodihydrofluorescein diacetate (Thermo Fisher Scientific) for 5 min.…”

Section: Measurement Of Intracellular Rosmentioning

confidence: 99%

“…SFII ( Fig. 1A) was identified by screening the natural compounds inhibiting osteoclast formation (EA289E-27-66-K7) (47). To further assess the inhibitory role of SFII in osteoclastogenesis, the concentration-dependent effect of SFII on the differentiation of BMMs to osteoclasts and the viability of these cells were explored.…”

Section: Sfii Inhibits Rankl-induced Osteoclast Differentiation and Nmentioning

confidence: 99%

“…Skullcapflavone II (SFII; 5,29-dihydroxy-6,7,8,69tetramethoxy-flavone) is one of the flavonoids isolated from the root of Scutellaria baicalensis, a medicinal herb used to treat inflammation and infection (41)(42)(43). SFII exhibits anti-inflammatory and antioxidant activities (44)(45)(46) and was recently isolated from the screening of natural compounds inhibiting RANKL-induced osteoclast formation (47). The present study demonstrates the molecular mechanism by which SFII inhibits osteoclastogenesis by regulating MAPKs, Src, and CREB through its antioxidant activity and attenuates the survival and resorption function by modulating the integrin-Src-p130Cas-Rho GTPase pathway in osteoclasts.…”

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confidence: 99%

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Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling

et al. 2018

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Many bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed to an increase in osteoclast number or activity; therefore, control of osteoclasts has significant clinical implications. This study shows how skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element-binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor-erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin β, Src, and p130 Crk-associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.-Lee, J., Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling.

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Section: Reagents and Antibodiesmentioning

confidence: 99%

Section: Rna Isolation Reverse Transcription and Real-time Pcr Analmentioning

confidence: 99%

Section: Measurement Of Intracellular Rosmentioning

confidence: 99%

Section: Sfii Inhibits Rankl-induced Osteoclast Differentiation and Nmentioning

confidence: 99%

mentioning

confidence: 99%

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Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling

et al. 2018

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Hesperetin suppresses RANKL‐induced osteoclastogenesis and ameliorates lipopolysaccharide‐induced bone loss

Liu

Dong

Gao

et al. 2018

Journal Cellular Physiology

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Destructive bone diseases caused by osteolysis are increasing in incidence. They are characterized by an excessive imbalance of osteoclast formation and activation. During osteolysis, the activation of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein kinase (MAPK) signaling pathways are triggered by receptor activator of NF‐κB ligand (RANKL), inflammatory factors, and oxidative stress. Previous studies have indicated that the common flavanone glycoside compound hesperetin exhibits anti‐inflammatory and antioxidant activity by inhibition of NF‐κB and MAPK signaling pathways. However, the direct relationship between hesperetin and osteolysis remain unclear. In the present study, we investigated the effects of hesperetin on lipopolysaccharide (LPS)‐induced osteoporosis and elucidated the related mechanisms. Hesperetin effectively suppressed RANKL‐induced osteoclastogenesis, osteoclastic bone resorption, and F‐actin ring formation in a dose‐dependent manner. It also significantly suppressed the expression of osteoclast‐specific markers including tartrate‐resistant acid phosphatase, matrix metalloproteinase‐9, cathepsin K, c‐Fos, and nuclear factor of activated T‐cells cytoplasmic 1. Furthermore, it inhibited osteoclastogenesis by inhibiting activation of NF‐κB and MAPK signaling, scavenging reactive oxygen species, and activating the nuclear factor E2 p45‐related factor 2/heme oxygenase 1 (Nrf2/HO‐1) signaling pathway. Consistent with in vitro results, hesperetin effectively ameliorated LPS‐induced bone loss, reduced osteoclast numbers, and decreased the RANKL/OPG ratio in vivo. As such, our results suggest that hesperetin may be a great candidate for developing a novel drug for destructive bone diseases such as periodontal disease, tumor bone metastasis, rheumatoid arthritis, and osteoporosis.

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Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis

Lee

Kim

et al. 2020

Journal Cellular Physiology

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Cinchonine (CN) has been known to exert antimalarial, antiplatelet, and antiobesity effects. It was also recently reported to inhibit transforming growth factor βactivated kinase 1 (TAK1) and protein kinase B (AKT) through binding to tumor necrosis factor receptor-associated factor 6 (TRAF6). However, its role in bone metabolism remains largely unknown. Here, we showed that CN inhibits osteoclast differentiation with decreased expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key determinant of osteoclastogenesis. Immunoblot and quantitative real-time polymerase chain reaction analysis as well as the reporter assay revealed that CN inhibits nuclear factor-κB and activator protein-1 by regulating TAK1. CN also attenuated the activation of AKT, cyclic AMP response element-binding protein, and peroxisome proliferator-activated receptor-γ coactivator 1β (PGC1β), an essential regulator of mitochondrial biogenesis. Collectively, these results suggested that CN may inhibit TRAF6-mediated TAK1 and AKT activation, which leads to downregulation of NFATc1 and PGC1β resulting in the suppression of osteoclast differentiation. Interestingly, CN not only inhibited the maturation and resorption function of differentiated osteoclasts but also promoted osteoblast differentiation. Furthermore, CN protected lipopolysaccharide-and ovariectomy-induced bone destruction in mouse models, suggesting its therapeutic potential for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

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Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast

Cited by 34 publications

References 54 publications

Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling

Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling

Hesperetin suppresses RANKL‐induced osteoclastogenesis and ameliorates lipopolysaccharide‐induced bone loss

Cinchonine inhibits osteoclast differentiation by regulating TAK1 and AKT, and promotes osteogenesis

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