High‑dose TGF‑β1 degrades human nucleus pulposus cells via ALK1‑Smad1/5/8 activation

Qu,Zhiqiang; Zhang,Fengxiang; Chen,Weiwei; Lin,Tao; Sun,Yongming

doi:10.3892/etm.2020.9088

High‑dose TGF‑β1 degrades human nucleus pulposus cells via ALK1‑Smad1/5/8 activation

Authors:
- Zhiqiang Qu
- Fengxiang Zhang
- Weiwei Chen
- Tao Lin
- Yongming Sun
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Affiliations: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of General Surgery, Tongliao City Hospital, Tongliao, Inner Mongolia 028000, P.R. China, Department of Disinfecting Supply Division, Tongliao City Hospital, Tongliao, Inner Mongolia 028000, P.R. China
Published online on: August 3, 2020 https://doi.org/10.3892/etm.2020.9088
Pages: 3661-3668
Copyright: © Qu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transforming growth factor β1 (TGF‑β1) can promote the proliferation and differentiation of intervertebral disc cells and participates in its repair process. However, whether TGF‑β1 engages in the process of disc degeneration has not yet been fully elucidated. The present study aimed to investigate the function of high‑dose TGF‑β1 on the metabolism of nucleus pulposus cells (NPCs). TGF‑β1 levels in human degenerative intervertebral disc tissues and tumor necrosis factor (TNF)‑α‑induced degenerative NPCs were analyzed. Furthermore, NPCs were treated with TGF‑β1 and inhibitors of TGF‑β1 receptors [ALK tyrosine kinase receptor (ALK) 1 and ALK5] to determine the effect of the receptors in the mediation of NPC degeneration. The NPC state was determined by the components of secretory collagen I/II, tissue inhibitor of metalloproteinase‑3 (TIMP‑3) and matrix metalloproteinase (MMP)‑13. The mRNA expression of Smad1/2/3/5/8, the downstream gene of TGF‑β1 mediated by ALK, was also measured. Results showed that TGF‑β1 and ALK1 were positively associated with the degree of degeneration of NP or NPCs in vitro, but negatively associated with ALK5. Furthermore, high‑doses of TGF‑β1 suppressed collagen II, but enhanced collagen I, TIMP‑3, MMP‑13, ALK1/5 and Smad1/2/3/5/8 expression. ALK5 inhibition induced the suppression of Smad2/3 and aggravated high‑dose TGF‑β1‑induced NPC degeneration, as shown by the reduction in collagen II and increase in collagen I, TIMP‑3 and MMP‑13. By contrast, ALK1 inhibition resulted in Smad1/5/8 suppression and alleviated high‑dose TGF‑β1‑induced NPC degeneration. Taken together, it was concluded that high‑doses of TGF‑β1 contributed to the degeneration of NPCs via the upregulation of ALK1 and Smad1/5/8.

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