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

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.

The isolation, structural characterization and anti-osteosarcoma activity of a water soluble polysaccharide from Agrimonia pilosa.

A homogenous polysaccharide (APP), with a molecular weight of 120 kDa, was isolated from the dried aerial parts of Agrimonia pilosa. Gas chromatography (GC) and GC-MS analysis revealed that APP has a backbone of 1,3-linked Glcp and 1,3, 6-linked Glcp, and branched with 1-linked Glcp terminal along the main chain in a relative ratio of 2:1:1. We investigated the response of human osteosarcoma U-2 OS cells to APP treatment. MTT result showed that APP significantly inhibited cell viability in a concentration dependent manner via induction of apoptotic death in U-2 OS cells, as determined by annexin V/propidium iodide (PI) staining. Western blot analysis also indicated that APP CRA increased in Bax/Bcl-2 ratios by up-regulating Bax expression and triggered the release of cytochrome c from mitochondria into the cytoplasm. Moreover, APP supplement induced the activation of caspase-3, and -9, but not caspase-8 in U-2 OS cells. Likewise, APP administration significantly suppressed tumor growth in BALB/C nude mice bearing U-2 OS xenograft tumors. All these results indicate that APP-induced apoptosis is associated with the activation of a caspase-3-mediated mitochondrial pathway.