Low-intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis

FEBS Open Bio. 2020 Mar;10(3):434-443. doi: 10.1002/2211-5463.12801. Epub 2020 Feb 5.


Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, was recently demonstrated to be an effective treatment for osteoarthritis (OA). Vascular endothelium growth factor A (VEGFA) has been found to be upregulated in the articular cartilage, synovium and subchondral bone of OA patients, leading to cartilage degeneration, synovitis and osteophyte formation. However, the functions and mechanisms of LIPUS in regulating chondrocyte-derived VEGFA expression are still unclear. In this study, we investigated whether LIPUS attenuated OA progression by (a) decreasing the percentage of VEGFA-positive cells in mouse articular cartilage destabilised through medial meniscus surgery and (b) relieving interleukin-1β-induced VEGFA expression in mouse primary chondrocytes. However, this function was negated by a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. In addition, we found that LIPUS ameliorated VEGFA-mediated disorders in cartilage extracellular matrix metabolism and chondrocyte hypertrophy during OA development. In conclusion, our data indicate a novel effect of LIPUS in regulating the expression of osteoarthritic chondrocyte-derived VEGFA through the suppression of p38 MAPK activity.

Keywords: articular cartilage; low-intensity pulsed ultrasound; osteoarthritis; vascular endothelium growth factor A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage / metabolism*
  • Cartilage / physiology
  • Cartilage Diseases / metabolism
  • Cartilage, Articular / metabolism
  • Chondrocytes / metabolism*
  • Extracellular Matrix / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Osteoarthritis / metabolism
  • Osteoarthritis / physiopathology
  • Osteophyte / metabolism
  • Protective Agents / metabolism
  • Protective Agents / pharmacology
  • Synovitis / metabolism
  • Ultrasonic Therapy / methods*
  • Ultrasonic Waves
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor A / physiology
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / pharmacology


  • Protective Agents
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • p38 Mitogen-Activated Protein Kinases