Open Access

Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration

  • Authors:
    • Meng Kong
    • Yiran Zhang
    • Mengxiong Song
    • Wenbin Cong
    • Changtong Gao
    • Jiajun Zhang
    • Shuo Han
    • Qihao Tu
    • Xuexiao Ma
  • View Affiliations

  • Published online on: May 10, 2021     https://doi.org/10.3892/ijmm.2021.4956
  • Article Number: 123
  • Copyright : © Kong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Previous studies have reported that the Ras homolog family member A (RhoA)/myocardin‑related transcription factor A (MRTF‑A) nuclear translocation axis positively regulates fibrogenesis induced by mechanical forces in various organ systems. The aim of the present study was to determine whether this signaling pathway was involved in the pathogenesis of nucleus pulposus (NP) fibrosis induced by mechanical overload during the progression of intervertebral disc degeneration (IVDD) and to confirm the alleviating effect of an MRTF‑A inhibitor in the treatment of IVDD. NP cells (NPCs) were cultured on substrates of different stiffness (2.9 and 41.7 KPa), which mimicked normal and overloaded microenvironments, and were treated with an inhibitor of MRTF‑A nuclear import, CCG‑1423. In addition, bipedal rats were established by clipping the forelimbs of rats at 1 month and gradually elevating the feeding trough, and in order to establish a long‑term overload‑induced model of IVDD, and their intervertebral discs were injected with CCG‑1423 in situ. Cell viability was determined by Cell Counting Kit‑8 assay, and protein expression was determined by western blotting, immunofluorescence and immunohistochemical staining. The results demonstrated that the viability of NPCs was not affected by the application of force or the inhibitor. In NPCs cultured on stiff matrices, MRTF‑A was mostly localized in the nucleus, and the expression levels of fibrotic proteins, including type I collagen, connective tissue growth factor and α‑smooth muscle cell actin, were upregulated compared with those in NPCs cultured on soft matrices. The levels of these proteins were reduced by CCG‑1423 treatment. In rats, 6 months of upright posture activated MRTF‑A nuclear‑cytoplasmic trafficking and fibrogenesis in the NP and induced IVDD; these effects were alleviated by CCG‑1423 treatment. In conclusion, the results of the present study demonstrated that the RhoA/MRTF‑A translocation pathway may promote mechanical overload‑induced fibrogenic activity in NP tissue and partially elucidated the molecular mechanisms underlying the occurrence of IVDD.
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July-2021
Volume 48 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kong M, Zhang Y, Song M, Cong W, Gao C, Zhang J, Han S, Tu Q and Ma X: Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration. Int J Mol Med 48: 123, 2021
APA
Kong, M., Zhang, Y., Song, M., Cong, W., Gao, C., Zhang, J. ... Ma, X. (2021). Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration. International Journal of Molecular Medicine, 48, 123. https://doi.org/10.3892/ijmm.2021.4956
MLA
Kong, M., Zhang, Y., Song, M., Cong, W., Gao, C., Zhang, J., Han, S., Tu, Q., Ma, X."Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration". International Journal of Molecular Medicine 48.1 (2021): 123.
Chicago
Kong, M., Zhang, Y., Song, M., Cong, W., Gao, C., Zhang, J., Han, S., Tu, Q., Ma, X."Myocardin‑related transcription factor A nuclear translocation contributes to mechanical overload‑induced nucleus pulposus fibrosis in rats with intervertebral disc degeneration". International Journal of Molecular Medicine 48, no. 1 (2021): 123. https://doi.org/10.3892/ijmm.2021.4956