Low‐Intensity Pulsed Ultrasound Treatment at an Early Osteoarthritis Stage Protects Rabbit Cartilage From Damage via the Integrin/Focal Adhesion Kinase/Mitogen‐Activated Protein Kinase Signaling Pathway

Objectives To investigate whether low‐intensity pulsed ultrasound (US) has different protective effects on early and late rabbit osteoarthritis cartilage via the integrin/focal adhesion kinase (FAK)/mitogen‐activated protein kinase (MAPK) signaling pathway. Methods Thirty‐six New Zealand White rabbits were divided into early control, early osteoarthritis, early treatment, late control, late osteoarthritis, and late treatment groups. The early and late osteoarthritis and treatment groups underwent anterior cruciate ligament transection. The remaining groups underwent sham operations with knee joint exposure. The early and late treatment groups were exposed to low‐intensity pulsed US 4 and 8 weeks after surgery. After 6 weeks of US exposure, pathologic changes on the articular surface of the femoral condyle were assessed by modified Mankin scores. Expression of type II collagen, matrix metalloproteinase, integrin β1, phosphorylated FAK, and MAPKs (including extracellular signal‐regulated kinase 1/2, MAPK 38, and c‐Jun N‐terminal kinase) was assessed by Western blot analysis. Results Cartilage damage was less severe in the early treatment group than the early osteoarthritis group. The Mankin score was significantly lower in the early treatment group than the early osteoarthritis group (P < .05). There was no significant difference in cartilage damage or Mankin score between the late treatment and late osteoarthritis groups. There was a significant increase in type II collagen expression but a significant decrease in matrix metalloproteinase 13 expression in the early treatment group compared to the early osteoarthritis group, whereas no significant difference was found between the late treatment and late osteoarthritis groups. Integrin β1 and phosphorylated FAK expression was significantly higher, and phosphorylated extracellular signal‐regulated kinase 1/2 and phosphorylated MAPK 38 expression was significantly lower in the early treatment group than the early osteoarthritis group. Conclusions Our findings indicate that low‐intensity pulsed US protects cartilage from damage in early‐stage osteoarthritis via the integrin/FAK/MAPK pathway.