Target-Specific Extracorporeal Shockwave Therapy Modulates TLR4/NF-κB/MMP13 Signaling Within the Joint Microenvironment to Improve Osteochondral Pathology in Patellofemoral Osteoarthritis.

BACKGROUND

Patellofemoral joint (PFJ) osteoarthritis (OA) is characterized by cartilage degeneration, subchondral bone remodeling, fat pad fibrosis, and chronic synovial inflammation. This study investigated the therapeutic effects of extracorporeal shockwave therapy (ESWT) applied to different anatomical targets in a rat PFJ OA model.

METHODS

PFJ OA was induced in rats and treated with ESWT targeted to either the tibial side (SWT) or femoral side (SWF). Micro-computed tomography, histological staining, and immunohistochemistry were used to assess structural changes, fibrosis, and inflammation. Molecular assessments showed the direct and indirecd effects of ESWT on the key inflammatory mediators, including IL-1β, NF-κB, RAGE, TLR4, and MyD88, and significantly reduced MMP13 expression in joint tissues.

RESULTS

ESWT significantly attenuated osteophyte formation, cystic changes, and sclerosis in the femoral and patellar bone. SWT showed superior improvement in bone volume fraction, trabecular thickness, and patellar bone integrity. Histologically, ESWT reduced cartilage degradation, fat pad fibrosis, and synovial inflammation. Molecular analyses revealed downregulation of pro-inflammatory mediators and MMP13, with SWT producing greater effects than SWF.

CONCLUSIONS

ESWT effectively mitigates structural damage, inflammation, and catabolic signaling in PFJ OA. Targeting the tibial side enhances therapeutic outcomes, highlighting ESWT as a promising non-invasive treatment strategy for PFJ OA.