Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages

Jiang, Chaolai; Zhou, Zubin; Lin, Yiwei; Shan, Haojie; Xia, Wenwen; Yin, Fuli; Wang, Nan; Zhou, Lihui; Gao, You-Shui; Yu, Xiaowei

doi:10.1016/j.intimp.2020.107345

Cited by 21 publications

(22 citation statements)

References 29 publications

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“…Emerging studies have shown that the level of proinflammatory cytokines is elevated in the serum of SIONFH patients [ 10 ]. Generally, glucocorticoid treatment is given to suppress inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…However, long-term or excess application of glucocorticoids functions as an activator for inflammation. The elevation of proinflammatory cytokines has been found in a mouse model of SIONFH [ 10 , 31 ]. Similar results were found in the rat model of SIONFH in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Following osteonecrosis, bone resorption mediated by osteoclasts surpasses bone formation by osteoblasts, leading to loss of subchondral trabecular bone. Elevated levels of proinflammatory cytokines have been found in SIONFH patients [ 10 ]. It is widely accepted that proinflammatory cytokines interfere with bone homeostasis [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats

Shen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 μg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats

Shen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Mouse macrophage cells (Raw264.7) were purchased from the Chinese Academy of Science cell bank. Mouse bone marrow macrophages (BMMs) and rat bone marrow mesenchymal stem cells (rBMSCs) were extracted and cultured in MEM-α (HyClone) containing 10% foetal bovine serum (FBS, Gibco) and 1% penicillin/streptomycin (Gibco) according to previous study [ 34 , 35 ]. After reaching 80% fusion, Raw264.7/BMMs were passed through a cell scraper, while rBMSCs were subjected to trypsin digestion.…”

Section: Methodsmentioning

confidence: 99%

A novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through osteoimmunomodulation

et al. 2022

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Background Femoral stem of titanium alloy has been widely used for hip arthroplasty with considerable efficacy; however, the application of this implant in patients with osteoporosis is limited due to excessive bone resorption. Macrophages participate in the regulation of inflammatory response and have been a topic of increasing research interest in implant field. However, few study has explored the link between macrophage polarization and osteogenic–osteoclastic differentiation. The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy. Method To improve the osteointegration under osteoporosis, we developed a hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold (PT). Biomimetic extracellular matrix (ECM) was constructed inside the interconnected pores of PT in micro-scale. And in nano-scale, a drug cargo icariin@Mg-MOF-74 (ICA@MOF) was wrapped in ECM-like structure that can control release of icariin and Mg2+. Results In this novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold, the macroporous structure provides mechanical support, the microporous structure facilitates cell adhesion and enhances biocompatibility, and the nanostructure plays a biological effect. We also demonstrate the formation of abundant new bone at peripheral and internal sites after intramedullary implantation of the biofunctionalized PT into the distal femur in osteoporotic rats. We further find that the controlled-release of icariin and Mg2+ from the biofunctionalized PT can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; thus, it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone. Conclusion The therapeutic potential of hierarchical PT implants containing controlled release system are effective in geriatric orthopaedic osseointegration. Graphical Abstract

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“…In addition, AS-IV inhibits progression and metastasis of lung cancer by regulating macrophage polarization through the AMPK signal ( 19 ). AS-IV also has been demonstrated to ameliorate steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages ( 20 ). However, during IBD progression, whether and how AS-IV exerts pro-resolving effects via remodeling intestinal macrophages development remains to be explored.…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling

et al. 2021

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Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.

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Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages

Cited by 21 publications

References 29 publications

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats

A novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through osteoimmunomodulation

Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling

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