Hypertrophic differentiation of mesenchymal stem cells is suppressed by xanthotoxin via the p38‑MAPK/HDAC4 pathway

Cao,Zhen; Bai,Yun; Liu,Chuan; Dou,Ce; Li,Jianmei; Xiang,Junyu; Zhao,Chunrong; Xie,Zhao; Xiang,Qiang; Dong,Shiwu

doi:10.3892/mmr.2017.6886

Hypertrophic differentiation of mesenchymal stem cells is suppressed by xanthotoxin via the p38‑MAPK/HDAC4 pathway

Authors:
- Zhen Cao
- Yun Bai
- Chuan Liu
- Ce Dou
- Jianmei Li
- Junyu Xiang
- Chunrong Zhao
- Zhao Xie
- Qiang Xiang
- Shiwu Dong
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Affiliations: Department of Anatomy, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, P.R. China, Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, P.R. China, Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China, Department of Emergency, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: June 29, 2017 https://doi.org/10.3892/mmr.2017.6886
Pages: 2740-2746
Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chondrocyte hypertrophy is a physiological process in endochondral ossification. However, the hypertrophic‑like alterations of chondrocytes at the articular surface may result in osteoarthritis (OA). In addition, the generation of fibrocartilage with a decreased biological function in tissue engineered cartilage, has been attributed to chondrocyte hypertrophy. Therefore, suppressing chondrocyte hypertrophy in OA and the associated regeneration of non‑active cartilage is of primary concern. The present study examined the effects of xanthotoxin (XAT), which is classified as a furanocoumarin, on chondrocyte hypertrophic differentiation of mesenchymal stem cells. Following XAT treatment, the expression levels of genes associated with chondrocyte hypertrophy were detected via immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. The results revealed that XAT inhibited the expression of various chondrocyte hypertrophic markers, including runt related transcription factor 2 (Runx2), matrix metalloproteinase 13 and collagen type X α1 chain. Further exploration indicated that XAT reduced the activation of p38‑mitogen activated protein kinase and then increased the expression of histone deacetylase 4 to suppress Runx2. The findings indicated that XAT maintained the chondrocyte phenotype in regenerated cartilage and therefore may exhibit promise as a potential drug for the treatment of OA in the future.

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