The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation

Deng,Ang; Zhang,Hongqi; Hu,Minyu; Liu,Shaohua; Wang,Yuxiang; Gao,Qile; Guo,Chaofeng

doi:10.3892/etm.2017.5458

The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation

Authors:
- Ang Deng
- Hongqi Zhang
- Minyu Hu
- Shaohua Liu
- Yuxiang Wang
- Qile Gao
- Chaofeng Guo
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Affiliations: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China, Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, Hunan 410078, P.R. China
Published online on: November 7, 2017 https://doi.org/10.3892/etm.2017.5458
Pages: 789-794
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The proliferative rate of chondrocytes affects bone elongation. Chondrocyte hypertrophy is required for endochondral bone formation as chondrocytes secrete factors required for osteoblast differentiation and maturation. Previous studies have demonstrated that the Indian hedgehog (Ihh) signaling pathway is a key regulator of skeletal development and homeostasis. The aim of the present study was to investigate the function of Ihh in chondrocyte proliferation and differentiation, as well as the underlying mechanisms. Ihh was knocked down in mouse chondrocyte cells using short hairpin RNA. Chondrocyte apoptosis and cell cycle arrest were assessed using flow cytometry and the results indicated that knockdown of Ihh significantly inhibited cell growth (P<0.05) and increased apoptosis (P<0.001) compared with negative control cells. Downregulation of Ihh also resulted in cell cycle arrest at G1 to S phase in chondrocytes. It was also observed that knockdown of Ihh decreased alkaline phosphatase activity and mineral deposition of chondrocytes. The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation may be associated with the transforming growth factor‑β/mothers against decapentaplegic and osteoprotegerin/receptor activator of nuclear factor κB ligand signaling pathway. The results of the present study suggest that chondrocyte‑derived Ihh is essential for maintaining bone growth plates and that manipulation of Ihh expression or its signaling components may be a novel therapeutic technique for the treatment of skeletal diseases, including achondroplasia.

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