Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption

Niu, Chenguang; Xiao, Fei; Yuan, Kai; Hu, Xuchen; Lin, Wei-Ming; Ma, Rui; Zhang, Xiaoling; Huang, Zhengwei

doi:10.3389/fphar.2017.00626

Cited by 23 publications

(24 citation statements)

References 58 publications

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“…In the present study, it was observed that silencing of AQP5 inhibited ERK1/2 signaling, consistent with the observations of prior studies (17,36). The downstream ERK signaling proteins c-Fos and CREB, which are present in the eukaryotic nucleus, are phosphorylated upon the activation of ERK signaling (37). The current study results also demonstrated that AQP5 silencing reduced the protein levels of c-Fos and p-CREB.…”

Section: Discussionsupporting

confidence: 92%

Silencing of aquaporinï¿½5 inhibits the growth of A549 lung cancer cells in vitro and in vivo

Zhou

et al. 2018

Int J Oncol

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The water channel protein aquaporin 5 (AQP5) is highly expressed in numerous tumors. However, its expression pattern and functions in lung cancer in humans remain unknown. In the present study, the role of AQP5 in the development of lung malignancies was examined. A short hairpin RNA construct targeting AQP5 mRNA was transfected into A549 cells to generate a lung cancer cell line in which AQP5 expression was stably silenced. In vitro and in vivo experiments were then performed to establish the effects of AQP5 on A549 cell apoptosis, proliferation and cell cycle progression. The results demonstrated that AQP5 silencing significantly inhibited the proliferation and promoted the apoptosis of A549 lung cancer cells in vitro and in vivo. In addition, it resulted in decreased activation of the extracellular signal-regulated kinase 1/2 signaling pathway in A549 cells, and reduced levels of the downstream proteins c‑Fos and phosphorylated cAMP response element-binding protein. Furthermore, inhibition of AQP5 expression effectively reduced the tumorigenicity of A549 cells in vivo. In conclusion, silencing of AQP5 suppressed the growth of A549 cells in vitro and in vivo, suggesting that it may serve as a therapeutic target in lung cancer.

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Section: Discussionsupporting

confidence: 92%

Silencing of aquaporinï¿½5 inhibits the growth of A549 lung cancer cells in vitro and in vivo

Zhou

et al. 2018

Int J Oncol

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“…30,31 LPS stimulates NF-kB activation and then leads to the release of inflammatory cytokines including TNF-α and IL-1, which induces osteoclast differentiation and function. 31,36 Our results demonstrated that daidzin greatly reduced bone resorption and TRAP-positive osteoclast number induced by LPS administration. Therefore, the inhibition of LPS-stimulated bone destruction could be attributed to the ability of daidzin to suppress NF-ĸB signaling activation.…”

Section: Discussionmentioning

confidence: 60%

Retracted: Daidzin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents LPS‐induced bone loss in vivo

Wei

Liang

Wei

et al. 2018

J of Cellular Biochemistry

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Osteoclasts are multinuclear giant cells responsible for bone resorption in bone loss diseases, including rheumatoid arthritis, periodontitis, and the aseptic loosening of orthopedic implants. Because of injurious side effects with currently available drugs, it is necessary to continue research novel bone‐protective therapies. Daidzin, a naturally occurring isoflavone found in leguminous plants, has numerous beneficial pharmacologic effects, including anti‐cancer, anti‐cholesterol, and anti‐angiocardiopathy, promoting osteoblasts differentiation, and even anti‐osteoporosis. However, the effect of daidzin on the regulation of osteoclast activity has not yet been investigated. In this study, our study showed that daidzin significantly inhibited receptor activator of nuclear factor‐kB ligand (RANKL)‐induced osteoclast differentiation of bone marrow macrophages and the hydroxyapatite‐resorbing activity of mature osteoclasts by inhibiting RANKL‐induced NF‐kB signaling pathway. In addition, daidzin could inhibit the expression of osteoclast marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene fos (c‐Fos), tartrate‐resistant acid phosphatase (TRAP), and cathepsin K (CTSK). Consistent with in vitro results, daidzin inhibited lipopolysaccharide‐induced bone loss by suppressing the osteoclast differentiation. Together our data demonstrated that daidzin inhibits RANKL‐induced osteoclastogenesis through suppressing NF‐ĸB signaling pathway and that daidzin is a promising agent in the treatment of osteolytic diseases.

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“…Based on these theories, a dose-dependent decrease in the number of TRAP +ve osteoclasts suggests a direct inhibitory effect of C-PC on the RANKL-induced osteoclastogenesis. This assay is considered the primary tool to investigate whether a non-cytotoxic compound has an anti-osteoclastogenic activity or not [35][36][37] .…”

Section: Discussionmentioning

confidence: 99%

C-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-κB activation

AlQranei

Aljohani

Majumdar

et al. 2020

Sci Rep

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Excessive bone loss occurs in inflammatory disorders such as periodontitis and osteoporosis. The underlying mechanism is related to the differentiation of macrophages into multinucleated giant osteoclasts and their bone resorptive activity. c-phycocyanin (c-pc) is a phycobiliprotein extracted from the blue-green algae, which has been shown to have various pharmacological effects. The role of C-PC on bone metabolism needs revelation. In this study, we determined the effectiveness of C-PC as an inhibitor of osteoclast differentiation, activity, and survival in vitro. We found that C-PC strongly inhibited the differentiation of macrophages to TRAP-positive osteoclasts, distinctive osteoclast specific podosomal organization, and dentine matrix resorption without any cytotoxicity. Also, it suppressed the expression of osteoclast specific markers, such as cathepsin K and integrin β3 at mRNA and protein levels. RANKL mediated signaling utilizes reactive oxygen species (ROS) for the differentiation of osteoclasts. C-PC attenuated RANKL stimulated ROS. Mechanistic studies indicate that C-PC has the potential to reduce osteoclast formation via blocking the degradation of cytosolic iκB-α and hence, the activation of downstream markers such as c-Fos and NFATc1. However, it does not have any effect on osteoblast-mediated bone formation in vitro. collectively, our data suggest that c-pc may be utilized as a therapeutic agent that can target bone loss mediated by excessive osteoclastic bone resorption without affecting osteoblastic activity in bone. Bone remodeling is a physiologically orchestrated process in which a simultaneous interplay between bone resorption and bone formation facilitates the development and maintenance of the skeletal tissues. However, an abnormal increased or decreased bone resorption rate is involved in the pathophysiology of multiple skeletal disorders 1,2. Osteolytic diseases, such as osteoporosis and periodontitis, carry a serious health concern. The net outcome of such pathological conditions is the loss of healthy and supportive bone due to the activation of osteoclasts 3,4. Osteoclasts are multinucleated-giant cells that are functionally recognized as primary bone-resorbing cells. Osteoclasts express tartrate-resistant acid phosphatase (TRAP), which is considered as one of the biomarkers. Osteoclasts are highly migratory cells, and their migration is dependent on rapid changes in their actin cytoskeletal structures. Osteoclasts do not have the focal adhesion attachment structures typical of other cells 5. Osteoclasts plated on glass coverslips demonstrated discrete dot-like podosome structures at the periphery, and, in some cells, podosomes were observed as ring-like structures 6,7. These types of podosomal or actin-ring like structures represent the unique characteristics that can demarcate the mature osteoclasts from osteoclast precursors. Osteoclasts are highly migrated cells and dependent on podosomes for their cellular motility 6,8,9 .

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Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption

Cited by 23 publications

References 58 publications

Silencing of aquaporinï¿½5 inhibits the growth of A549 lung cancer cells in vitro and in vivo

Silencing of aquaporinï¿½5 inhibits the growth of A549 lung cancer cells in vitro and in vivo

Retracted: Daidzin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents LPS‐induced bone loss in vivo

C-phycocyanin attenuates RANKL-induced osteoclastogenesis and bone resorption in vitro through inhibiting ROS levels, NFATc1 and NF-κB activation

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