Inhibitory effect of low‑intensity pulsed ultrasound on the fibrosis of the infrapatellar fat pad through the regulation of HIF‑1α in a carrageenan‑induced knee osteoarthritis rat model

  • Authors:
    • Takashi Kitagawa
    • Hirohisa Kawahata
    • Motokuni Aoki
    • Shintarou Kudo
  • View Affiliations

  • Published online on: August 9, 2022     https://doi.org/10.3892/br.2022.1562
  • Article Number: 79
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Fibrotic changes in the infrapatellar fat pad (IFP) are involved in the pathogenesis of knee osteoarthritis (KOA). HIF‑1α is a transcription factor that is activated during hypoxia and is suggested to play a role in fibrosis in various organs. However, its participation in the fibrotic changes in IFP remains unclear. Therefore, we investigated the role of HIF‑1α in IFP fibrosis using a carrageenan‑induced KOA rat model and evaluated the potential of low‑intensity pulsed ultrasound (LIPUS) as a novel treatment for KOA. A rat model was prepared by intra‑articular injection of 0.5% carrageenan (50 µl) using 8‑week‑old male Wistar rats. Fibrosis of the IFP was evaluated histologically by hematoxylin and eosin and Sirius Red staining at 1 and 2 weeks after intra‑articular injection. The mRNA expression levels of HIF‑1α and fibrosis‑related molecules, CTGF and VEGF, were analyzed using reverse transcription‑quantitative PCR, and the DNA binding activity of HIF‑1α was assessed using a binding assay. In addition, the effect of irradiation with LIPUS on the fibrosis of IFP was verified. Histological studies demonstrated a significant increase in the fibrosis of IFP 1 and 2 weeks after intra‑articular injection of carrageenan, accompanied by overexpression of CTGF and VEGF, which was followed by upregulation of transcriptional activation of HIF‑1α. Moreover, intervention with LIPUS for 2 weeks after injection of carrageenan attenuated fibrosis of IFP, accompanied by a significant reduction in the transcriptional activation of HIF‑1α and decreased the gene expression levels of HIF‑1α, CTGF, and VEGF. The present study demonstrated that activation of HIF‑1α promoted fibrosis of IFP in carrageenan‑induced arthritis in rats and that intervention with LIPUS decreased the activity of HIF‑1α and inhibited fibrosis. These results suggest that LIPUS may serve as a novel approach for the treatment of KOA, through its modulation of HIF‑1α.

Related Articles

Journal Cover

October-2022
Volume 17 Issue 4

Print ISSN: 2049-9434
Online ISSN:2049-9442

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kitagawa T, Kawahata H, Aoki M and Kudo S: Inhibitory effect of low‑intensity pulsed ultrasound on the fibrosis of the infrapatellar fat pad through the regulation of HIF‑1α in a carrageenan‑induced knee osteoarthritis rat model. Biomed Rep 17: 79, 2022
APA
Kitagawa, T., Kawahata, H., Aoki, M., & Kudo, S. (2022). Inhibitory effect of low‑intensity pulsed ultrasound on the fibrosis of the infrapatellar fat pad through the regulation of HIF‑1α in a carrageenan‑induced knee osteoarthritis rat model. Biomedical Reports, 17, 79. https://doi.org/10.3892/br.2022.1562
MLA
Kitagawa, T., Kawahata, H., Aoki, M., Kudo, S."Inhibitory effect of low‑intensity pulsed ultrasound on the fibrosis of the infrapatellar fat pad through the regulation of HIF‑1α in a carrageenan‑induced knee osteoarthritis rat model". Biomedical Reports 17.4 (2022): 79.
Chicago
Kitagawa, T., Kawahata, H., Aoki, M., Kudo, S."Inhibitory effect of low‑intensity pulsed ultrasound on the fibrosis of the infrapatellar fat pad through the regulation of HIF‑1α in a carrageenan‑induced knee osteoarthritis rat model". Biomedical Reports 17, no. 4 (2022): 79. https://doi.org/10.3892/br.2022.1562