Open Access

Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis

  • Authors:
    • Xiaoxin He
    • Kuanmin Tian
    • Xue Lin
    • Xiaolei Chen
    • Yajing Su
    • Zhidong Lu
    • Zhirong Chen
    • Liang Zhang
    • Peng Li
    • Long Ma
    • Gangning Feng
    • Xin Zhao
    • Zhibin Lan
    • Chen Zhang
    • Di Xue
    • Qunhua Jin
  • View Affiliations

  • Published online on: August 6, 2024     https://doi.org/10.3892/ijmm.2024.5410
  • Article Number: 86
  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT‑PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter‑EC adhesion proteins (zona occludens‑1, connexin 43 and Vascular endothelial‑Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl‑CoA synthase long‑chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter‑EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.
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October-2024
Volume 54 Issue 4

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

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Copy and paste a formatted citation
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Spandidos Publications style
He X, Tian K, Lin X, Chen X, Su Y, Lu Z, Chen Z, Zhang L, Li P, Ma L, Ma L, et al: Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis. Int J Mol Med 54: 86, 2024.
APA
He, X., Tian, K., Lin, X., Chen, X., Su, Y., Lu, Z. ... Jin, Q. (2024). Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis. International Journal of Molecular Medicine, 54, 86. https://doi.org/10.3892/ijmm.2024.5410
MLA
He, X., Tian, K., Lin, X., Chen, X., Su, Y., Lu, Z., Chen, Z., Zhang, L., Li, P., Ma, L., Feng, G., Zhao, X., Lan, Z., Zhang, C., Xue, D., Jin, Q."Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis". International Journal of Molecular Medicine 54.4 (2024): 86.
Chicago
He, X., Tian, K., Lin, X., Chen, X., Su, Y., Lu, Z., Chen, Z., Zhang, L., Li, P., Ma, L., Feng, G., Zhao, X., Lan, Z., Zhang, C., Xue, D., Jin, Q."Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis". International Journal of Molecular Medicine 54, no. 4 (2024): 86. https://doi.org/10.3892/ijmm.2024.5410