Sophocarpine attenuates wear particle‐induced implant loosening by inhibiting osteoclastogenesis and bone resorption<i>via</i>suppression of the NF‐κB signalling pathway in a rat model

Zhou, Chenhe; Shi, Zhijun; Meng, Jinghui; Hu, Bin; Zhao, Chenchen; Yang, Yingxin; Yu, Wei; Zexin, Chen; Heng, Boon Chin; Parkman, Virginia-Jeni Akila; Jiang, Shuai; Zhu, Hanxiao; Wu, Haobo; Shen, Wei; Yan, Shigui

doi:10.1111/bph.14092

Cited by 28 publications

(32 citation statements)

References 68 publications

(90 reference statements)

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“…Subsequently, mature osteoclasts undergo polarization and structural changes to produce a tight sealing zone. Secretion of acids and proteolytic enzymes into this sealing zone results in the dissolution and degradation of the underlying bone …”

Section: Introductionmentioning

confidence: 99%

“…Several recent studies have focused on natural compounds because of their pharmacological activity against human diseases. Over several years, our group has screened natural compounds for treating osteoclast‐related diseases . Stachydrine (STA), a bioactive constituent extracted from a medicinal herb Leonurus heterophyllus Sweet, has extensive pharmacological properties, including antioxidant, anti‐inflammatory, anticancer and cardioprotective properties .…”

Section: Introductionmentioning

confidence: 99%

“…Secretion of acids and proteolytic enzymes into this sealing zone results in the dissolution and degradation of the underlying bone. 13,14 Several recent studies have focused on natural compounds because of their pharmacological activity against human diseases. Over several years, our group has screened natural compounds for treating osteoclast-related diseases.…”

mentioning

confidence: 99%

“…Over several years, our group has screened natural compounds for treating osteoclast-related diseases. [13][14][15][16] Stachydrine (STA), a bioactive constituent extracted from a medicinal herb Leonurus heterophyllus Sweet, has extensive pharmacological properties, including antioxidant, anti-inflammatory, anticancer and cardioprotective properties. [17][18][19][20] Recent studies have reported that STA inhibits NF-κB and MAPK pathways in different cell types.…”

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confidence: 99%

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Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Meng

Zhou

Zhang

et al. 2019

J Cellular Molecular Medi

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Osteoclast overactivation‐induced imbalance in bone remodelling leads to pathological bone destruction, which is a characteristic of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, periprosthetic osteolysis and periodontitis. Natural compounds that suppress osteoclast formation and function have therapeutic potential for treating these diseases. Stachydrine (STA) is a bioactive alkaloid isolated from Leonurus heterophyllus Sweet and possesses antioxidant, anti‐inflammatory, anticancer and cardioprotective properties. However, its effects on osteoclast formation and function have been rarely described. In the present study, we found that STA suppressed receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast formation and bone resorption, and reduced osteoclast‐related gene expression in vitro. Mechanistically, STA inhibited RANKL‐induced activation of NF‐κB and Akt signalling, thus suppressing nuclear factor of activated T cells c1 induction and nuclear translocation. In addition, STA alleviated bone loss and reduced osteoclast number in a murine model of LPS‐induced inflammatory bone loss. STA also inhibited the activities of NF‐κB and NFATc1 in vivo. Together, these results suggest that STA effectively inhibits osteoclastogenesis both in vitro and in vivo and therefore is a potential option for treating osteoclast‐related diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Meng

Zhou

Zhang

et al. 2019

J Cellular Molecular Medi

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“…Besides, NF-κB activation contributes to osteoclast differentiation and maturation vis the binding of RANKL and osteoclastassociated RANK [14]. A number of researchers have reported that repressing NF-κB signaling pathway activation could attenuate wear debris-induced osteolysis [15][16][17]. Our previous study has proved that the PI3K/Akt pathway plays a positive role in the regulation of activating macrophages by wear particles.…”

Section: Introductionmentioning

confidence: 99%

The USP14–NLRC5 pathway inhibits titanium particle–induced osteolysis in mice by suppressing NF-κB and PI3K/AKT activities

Fang¹,

Fu²,

et al. 2020

Journal of Biological Chemistry

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Total hip arthroplasty (THA) is a widely-used surgical intervention for treating patients with end-stage degenerative and inflammatory osteoarthropathy. However, wear particles from the artificial titanium joint can induce osteolysis, limiting the long-term survivorship of THA. Monocyte/macrophage lineage cells are the key players in the response to wear particles, and the proinflammatory NF-κB and phosphoinositide 3-kinase (PI3K)–AKT Ser/Thr kinase (AKT)-signaling pathways have been shown to be the most important contributors to wear particle–induced osteolysis. In contrast, ubiquitin-specific protease 14 (USP14) specifically removes the polyubiquitin chains from the nucleotide-binding and oligomerization domain (NOD)-like receptor family Caspase recruitment domain (CARD)–containing 5 (NLRC5) and thereby enhances the NLRC5-mediated inhibition of NF-κB signaling. In this study, we aimed to clarify the role of the USP14–NLRC5 pathway in wear particle–induced osteolysis in vitro and in vivo. We found that NLRC5 or USP14 overexpression inhibits titanium particle–induced proinflammatory tumor necrosis factor α (TNFα) production and NF-κB pathway activation, and it also decreases M1 macrophage polarization and PI3K/AKT pathway activation. Of note, NLRC5 and USP14 overexpression attenuated titanium particle–induced cranial osteolysis in mice. In conclusion, the findings of our study indicate that the USP14–NLRC5 pathway inhibits titanium particle–induced osteolysis by suppressing the NF-κB and PI3K/AKT pathways both in vitro and in vivo.

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Osteolysis After Total Hip Arthroplasty: Basic Science

Vallés

Vilaboa

2018

Acetabular Revision Surgery in Major Bone Defects

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Sophocarpine attenuates wear particle‐induced implant loosening by inhibiting osteoclastogenesis and bone resorptionviasuppression of the NF‐κB signalling pathway in a rat model

Abstract: SPC can prevent implant loosening through inhibiting osteoclast formation and bone resorption. Thus, SPC might be a novel therapeutic agent to prevent prosthesis loosening and for osteolytic diseases.

Cited by 28 publications

References 68 publications

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

Stachydrine prevents LPS‐induced bone loss by inhibiting osteoclastogenesis via NF‐κB and Akt signalling

The USP14–NLRC5 pathway inhibits titanium particle–induced osteolysis in mice by suppressing NF-κB and PI3K/AKT activities

Osteolysis After Total Hip Arthroplasty: Basic Science

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