Curcumin prevents osteocyte apoptosis by inhibiting M1-type macrophage polarization in mice model of glucocorticoid-associated osteonecrosis of the femoral head

J Orthop Res. 2020 Sep;38(9):2020-2030. doi: 10.1002/jor.24619. Epub 2020 Feb 13.

Abstract

Inflammation is a contributing factor in osteocyte apoptosis, which is strongly associated with the development of glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Curcumin is a naturally derived drug that regulates immunity and inhibits inflammation. This study aimed to examine the capacity of curcumin to prevent osteocyte apoptosis and GA-ONFH, while elucidating possible mechanisms of action. C57/BL6 female mice were divided into control, GA-ONFH, and curcumin-treated GA-ONFH groups. We determined the effect of curcumin on the polarization of RAW264.7 and the apoptosis of MLO-Y4 cells. We found that curcumin reduced the infiltration of M1-type macrophages in the femoral heads and alleviated systemic inflammation in GA-ONFH models. Additionally, curcumin decreased the apoptosis of osteocytes in the femoral heads and the ratio of GA-ONFH in mice. Further, in vitro curcumin intervention inhibited M1-type polarization via the Janus kinase1/2-signal transducer and activator of transcription protein1 (JAK1/2-STAT1) pathway. Taken together, this study demonstrates that curcumin is effective in preventing osteocyte apoptosis and the development of GA-ONFH in a mouse model. Curcumin prevents inflammatory-mediated apoptosis of osteocytes in part through inhibition of M1 polarization through the JAK1/2-STAT1 pathway. These findings provide novel insights as well as a potential preventive agent for GA-ONFH. This article is protected by copyright. All rights reserved.

Keywords: apoptosis; curcumin; glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH); macrophages; osteocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Apoptosis / drug effects
  • Curcuma
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Female
  • Femur Head Necrosis / chemically induced
  • Femur Head Necrosis / enzymology
  • Femur Head Necrosis / prevention & control*
  • Glucocorticoids
  • Janus Kinases / metabolism
  • Macrophages / drug effects*
  • Mice, Inbred C57BL
  • Osteocytes / drug effects*
  • Phytotherapy
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Glucocorticoids
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Janus Kinases
  • Curcumin