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Highdose TGFβ1 degrades human nucleus pulposus cells via ALK1Smad1/5/8 activation

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Transforming growth factor β1 (TGFβ1) can promote the proliferation and differentiation of intervertebral disc cells and participates in its repair process. However, whether TGFβ1 engages in the process of disc degeneration has not yet been fully elucidated. The present study aimed to investigate the function of highdose TGFβ1 on the metabolism of nucleus pulposus cells (NPCs). TGFβ1 levels in human degenerative intervertebral disc tissues and tumor necrosis factor (TNF)αinduced degenerative NPCs were analyzed. Furthermore, NPCs were treated with TGFβ1 and inhibitors of TGFβ1 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 metalloproteinase3 (TIMP3) and matrix metalloproteinase (MMP)13. The mRNA expression of Smad1/2/3/5/8, the downstream gene of TGFβ1 mediated by ALK, was also measured. Results showed that TGFβ1 and ALK1 were positively associated with the degree of degeneration of NP or NPCs in┬ávitro, but negatively associated with ALK5. Furthermore, highdoses of TGFβ1 suppressed collagen II, but enhanced collagen I, TIMP3, MMP13, ALK1/5 and Smad1/2/3/5/8 expression. ALK5 inhibition induced the suppression of Smad2/3 and aggravated highdose TGFβ1induced NPC degeneration, as shown by the reduction in collagen II and increase in collagen I, TIMP3 and MMP13. By contrast, ALK1 inhibition resulted in Smad1/5/8 suppression and alleviated highdose TGFβ1induced NPC degeneration. Taken together, it was concluded that highdoses of TGFβ1 contributed to the degeneration of NPCs via the upregulation of ALK1 and Smad1/5/8.
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Document Type: Research Article

Affiliations: 1: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China 2: Department of General Surgery, Tongliao City Hospital, Tongliao, Inner Mongolia 028000, P.R. China 3: Department of Disinfecting Supply Division, Tongliao City Hospital, Tongliao, Inner Mongolia 028000, P.R. China

Publication date: October 1, 2020

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  • Experimental and Therapeutic Medicine aims to ensure the expedient publication, in both print and electronic format, of studies relating to biology, gene therapy, infectious disease, microbiology, molecular cardiology and molecular surgery. The journal welcomes studies pertaining to all aspects of molecular medicine, and studies relating to in vitro or in vivo experimental model systems relevant to the mechanisms of disease are also included.

    All materials submitted to this journal undergo the appropriate review via referees who are experts in this field. All materials submitted follow international guidelines with regard to approval of experiments on humans and animals.
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