PMID- 33563553 OWN - NLM STAT- MEDLINE DCOM- 20210603 LR - 20240226 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 93 DP - 2021 Apr TI - Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages. PG - 107345 LID - S1567-5769(20)33813-3 [pii] LID - 10.1016/j.intimp.2020.107345 [doi] AB - Osteonecrosis of the femoral head (ON-FH) is a common complication of steroid use. Pro-inflammatory macrophages play a crucial role in the apoptosis of osteocytes. The objective of the study was to evaluate a plant extract astragaloside IV (AS-IV) in treating ON-FN. Bone-marrow-derived macrophages (BMDMs) were treated with lipopolysaccharides (LPS), IFN-gamma or IL-4 to induce M1 and M2-like phenotypes. Quantitative real-time PCR and Western blot were used to examine M1 and M2 phenotypic markers. Flow cytometry was used to analyze MHC II, CD206, F4/80, and CD11b levels and cell apoptosis. Glucocorticoid was used to induce ON-FN in mice. TNF-alpha and IL-1beta levels in femoral head were determined using enzyme-linked immunosorbent assay. AS-IV repolarized macrophages from M1 to M2 phenotypes. Culture medium from AS-IV treated M1 macrophages induced less cell apoptosis osteocytes compared to that from untreated M1 macrophages. In ON-FH mice, the ratio of M1 macrophages was decreased in the femoral head by AS-IV, concomitant with a decrease in TNF-alpha and IL-1beta levels. AS-IV is effective in alleviating ON-FH through its effects in repolarizing macrophages from M1-like phenotype to M2-like phenotype, promoting survival of osteocytes, reducing arthritic symptoms, and decreasing inflammatory cytokines. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Jiang, Chaolai AU - Jiang C AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Zhou, Zubin AU - Zhou Z AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Lin, Yiwei AU - Lin Y AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Shan, Haojie AU - Shan H AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Xia, Wenyang AU - Xia W AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Yin, Fuli AU - Yin F AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Wang, Nan AU - Wang N AD - Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. FAU - Zhou, Lihui AU - Zhou L AD - Department of Orthopaedic Surgery, Xiangshan First People's Hospital, Ningbo 315700, Zhejiang, China. FAU - Gao, Youshui AU - Gao Y AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. FAU - Yu, Xiaowei AU - Yu X AD - Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: yuxw@sjtu.edu.cn. LA - eng PT - Journal Article DEP - 20210206 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Glucocorticoids) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - 3A592W8XKE (astragaloside A) SB - IM MH - Animals MH - Cells, Cultured MH - Female MH - Femur Head/drug effects/immunology MH - Femur Head Necrosis/chemically induced/*drug therapy/immunology MH - Glucocorticoids MH - Macrophages/*drug effects/immunology MH - Mice, Inbred C57BL MH - Phenotype MH - Saponins/pharmacology/*therapeutic use MH - Triterpenes/pharmacology/*therapeutic use MH - Mice OTO - NOTNLM OT - Astragaloside IV OT - Inflammation OT - Macrophages OT - Osteonecrosis of the femoral head OT - Repolarization EDAT- 2021/02/11 06:00 MHDA- 2021/06/04 06:00 CRDT- 2021/02/10 05:39 PHST- 2020/07/24 00:00 [received] PHST- 2020/12/21 00:00 [revised] PHST- 2020/12/24 00:00 [accepted] PHST- 2021/02/11 06:00 [pubmed] PHST- 2021/06/04 06:00 [medline] PHST- 2021/02/10 05:39 [entrez] AID - S1567-5769(20)33813-3 [pii] AID - 10.1016/j.intimp.2020.107345 [doi] PST - ppublish SO - Int Immunopharmacol. 2021 Apr;93:107345. doi: 10.1016/j.intimp.2020.107345. Epub 2021 Feb 6.