Therapeutic mechanisms of ibuprofen, prednisone and betamethasone in osteoarthritis

Sun,Fenglong; Zhang,Yaohua; Li,Qiang

doi:10.3892/mmr.2016.6068

Therapeutic mechanisms of ibuprofen, prednisone and betamethasone in osteoarthritis

Authors:
- Fenglong Sun
- Yaohua Zhang
- Qiang Li
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Affiliations: Department of Orthopedics, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
Published online on: December 22, 2016 https://doi.org/10.3892/mmr.2016.6068
Pages: 981-987

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Abstract

The present study aimed to investigate the therapeutic mechanisms of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids in osteoarthritis (OA). The CHON‑002 human chondrocyte cell line was used in the study. The levels of the cytokines, interleukin (IL)‑1β, IL‑6, IL‑8 and IL‑10, released by cells treated with tumor necrosis factor‑α (TNF‑α) were determined by ELISA. Levels of collagen I, aggrecan, matrix metalloproteinase (MMP)‑1, MMP‑13, signal transducer and activator of transcription (STAT) 3, nuclear factor‑κB (NF‑κB) subunit p65 and inhibitory subunit of NF‑κB (IκB) following treatment with IL‑1β, IL‑6, IL‑8 or IL‑10 were assessed by western blot. Levels of IL‑6 and IL‑8 were measured by ELISA following administration of TNF‑α combined with certain drugs. In addition, these parameters were evaluated by western blot following incubation with drugs in combination with IL‑6 or IL‑8 and after knockdown of STAT3, by addition of small interfering RNA (siRNA)‑STAT3 (siSTAT3), an inhibitor of the proteasome (MG132) or both. IL‑1β, IL‑6, IL‑8 and IL-10 were upregulated by TNF‑α. Addition of IL‑6 or IL‑8 led to increased collagen I, MMP‑1 and MMP‑13 protein levels, and also promoted STAT3 phosphorylation and increased the expression of NF‑κB subunit p65, but had no effect on aggrecan protein levels. When siSTAT3 and MG132 treatment was combined, levels of collagen I, MMP‑1 and MMP‑13 were reduced. Additionally, levels of IL‑6 and IL‑8 were significantly decreased by prednisone, ibuprofen and betamethasone. However, no significant differences were observed following treatment with piroxicam or indomethacin. In combination with IL‑6 or IL‑8, prednisone, ibuprofen and betamethasone significantly reduced the levels of collagen I, MMP‑1 and MMP‑13, and inactivated NF‑κB and STAT3 pathways. In conclusion, prednisone, ibuprofen and betamethasone may prevent OA by suppressing the expression of IL‑6 and IL‑8, subsequently inactivating NF‑κB and STAT3 pathways, and ultimately, leading to decreased levels of collagen I, MMP‑1, and MMP‑13.

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