Wei Huang

Excessive use of glucocorticoids (GCs) may cause adverse effects on the skeletal system in children. However, only a few studies have reported the effects of GCs on the epiphyseal cartilage. This study aimed to uncover the subsequent epiphyseal cartilage changes of immature femoral heads after excessive GC treatment in a mouse model and explain the pathological changes preliminarily. Female C57BL/6 mice were divided into control and model (excessive GC treatment) groups. The structure of the femoral heads was evaluated by using micro-computed tomography, hematoxylin-eosin staining, and safranin staining analyses. Immunohistochemistry was used to detect angiogenesis and cartilage metabolism. Western blotting and TUNEL staining were used to examine epiphyseal cartilage chondrocyte apoptosis. Primary chondrocytes were isolated from the femoral heads of healthy mice for in vitro studies. The effects of GCs on chondrocyte apoptosis and metabolism were determined by flow cytometry and Western blotting. The epiphyseal cartilage ossification had started at 4 weeks posttreatment in a portion of mice; the ossification presented as a sequential process in the model group, while the epiphyseal cartilage maintained an unossified state in the control group. Vascular invasion into the epiphyseal cartilage of the model mice was observed at 4 weeks posttreatment. GCs induced chondrocyte apoptosis and altered chondrocyte metabolism in the epiphyseal cartilage. The epiphyseal cartilage ossification accelerated in the femoral heads of female C57BL/6 mice after excessive GC treatment. Increased chondrocyte apoptosis, altered chondrocyte metabolism, as well as increased vascular invasion, are the potential factors influencing epiphyseal cartilage ossification.

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 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 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.