Saikosaponin a inhibits RANKL-induced osteoclastogenesis by suppressing NF-κB and MAPK pathways

Zhou, Chi; Wang, Xinyang; He, Wei; Wang, Haibin; Chen, Qunqun; Hou-pan, Song

doi:10.1016/j.intimp.2015.01.010

Cited by 36 publications

(24 citation statements)

References 34 publications

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“…As it has been reported that mitogen-activated protein kinases (MAPKs) and nucleur factor- κ B (NF- κ B) are the key downstream pathways of RANKL in the process of osteoclastogenesis, 29, 30, 31 we first explore the effects of DFO on RANKL-induced these intracellular signalings during the osteoclast differentiation. BMMs were preincubated with 50 μ M DFO, followed by stimulating with RANKL for the indicated time points.…”

Section: Resultsmentioning

confidence: 99%

Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1

et al. 2016

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As wear particles-induced osteolysis still remains the leading cause of early implant loosening in endoprosthetic surgery, and promotion of osteoclastogenesis by wear particles has been confirmed to be responsible for osteolysis. Therapeutic agents targeting osteoclasts formation are considered for the treatment of wear particles-induced osteolysis. In the present study, we demonstrated for the first time that desferrioxamine (DFO), a powerful iron chelator, could significantly alleviate osteolysis in an ultrahigh-molecular-weight polyethylene (UHMWPE) particles-induced mice calvaria osteolysis model. Furthermore, DFO attenuated calvaria osteolysis by restraining enhanced inflammatory osteoclastogenesis induced by UHMWPE particles. Consistent with the in vivo results, we found DFO was also able to inhibit osteoclastogenesis in a dose-dependent manner in vitro, as evidenced by reduction of osteoclasts formation and suppression of osteoclast specific genes expression. In addition, DFO dampened osteoclasts differentiation and formation at early stage but not at late stage. Mechanistically, the reduction of osteoclastogenesis by DFO was due to increased heme oxygenase-1 (HO-1) expression, as decreased osteoclasts formation induced by DFO was significantly restored after HO-1 was silenced by siRNA, while HO-1 agonist COPP treatment enhanced DFO-induced osteoclastogenesis inhibition. In addition, blocking of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway promoted DFO-induced HO-1 expression, implicating that p38 signaling pathway was involved in DFO-mediated HO-1 expression. Taken together, our results suggested that DFO inhibited UHMWPE particles-induced osteolysis by restraining inflammatory osteoclastogenesis through upregulation of HO-1 via p38MAPK pathway. Thus, DFO might be used as an innovative and safe therapeutic alternative for treating wear particles-induced aseptic loosening.

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Section: Resultsmentioning

confidence: 99%

Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1

et al. 2016

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“…In vitro study revealed that saikosaponin A suppressed osteoclastogenesis in C57/BL6 mice bone marrow monocytes and mediated osteoclast differentiation through inhibiting RANKL-induced p38, ERK, JNK, and NF-κB activation in murine RAW264.7 cell line (92). Saikosaponins showed a potent anti-inflammatory and anti-osteoporotic effect as safe and effective agents for management of postmenopausal osteoporosis.…”

Section: Saikosaponinsmentioning

confidence: 98%

Chinese single herbs and active ingredients for postmenopausal osteoporosis: From preclinical evidence to action mechanism

Lin

Wang

Zhang

et al. 2017

BST

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“…In contrast, other saikosaponins such as SSa and SSd have been proved possess anti-inflammatory activities [17]. For example, SSa exerts anti-inflammatory activities by inhibiting the expression of pro-inflammatory cytokines and regulating inflammation-associated signal pathways, such as MAPK pathway and nuclear factor-κB (NF-κB) pathway [39]. In addition to inflammation, the contrary role of different saikosaponins in other signaling pathway was also be frequently observed.…”

Section: Discussionmentioning

confidence: 99%

Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis

Pan

et al. 2019

Inflamm. Res.

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Objective Saikosaponin c (SSc), a compound purified from the traditional Chinese herb of Radix Bupleuri was previously identified to exhibit anti-HBV replication activity. However, the mechanism through which SSc acts against HBV remains unknown. In this study, we investigated the mechanism of SSc mediated anti-HBV activity. Methods HepG2.2.15 cells were cultured at 37 ℃ in the presence of 1-40 μg/mL of SSc or DMSO as a control. The expression profile of HBV markers, cytokines, HNF1α and HNF4α were investigated by real-time quantitative PCR, Elisa, Western blot and Dot blotting. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells was mediated by two small siRNAs specifically targeting HNF1α or HNF4α. Results We found that SSc stimulates IL-6 expression, leading to attenuated HNF1α and HNF4α expression, which further mediates suppression of HBV pgRNA synthesis. Knockdown of HNF1α or HNF4α in HepG2.2.15 cells by RNA interference abrogates SSc's anti-HBV role. Moreover, SSc is effective to both wild-type and drug-resistant HBV mutants. Conclusion SSc inhibits pgRNA synthesis by targeting HNF1α and HNF4α. These results indicate that SSc acts as a promising compound for modulating pgRNA transcription in the therapeutic strategies against HBV infection.

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Saikosaponin a inhibits RANKL-induced osteoclastogenesis by suppressing NF-κB and MAPK pathways

Cited by 36 publications

References 34 publications

Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1

Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1

Chinese single herbs and active ingredients for postmenopausal osteoporosis: From preclinical evidence to action mechanism

Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis

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