Long-term mechanical loading aggravates osteoarthritis through a pro-apoptotic inflammatory microenvironment.

Area of Science:

• Biomedical Engineering
• Orthopedics
• Cartilage Biology

Background:

• Articular cartilage health depends on mechanical loading, but excessive or insufficient loads can cause damage.
• The impact of exercise on early osteoarthritis (OA) is debated, especially for active individuals.

Purpose of the Study:

• To investigate the effects of prolonged moderate mechanical loading on articular cartilage.
• To explore the role of nerve growth factor (NGF) in cartilage response to mechanical stress in early OA.

Main Methods:

• Established in vitro and in vivo models of prolonged moderate mechanical loading (7.5% strain, 1 Hz).
• Analyzed human cartilage from weight-bearing and non-weight-bearing regions using RNA sequencing.
• Utilized immunofluorescence staining to detect NGF accumulation.

Main Results:

• Prolonged loading (≥12 h) significantly increased chondrocyte apoptosis (2.3-fold) and reduced matrix markers (SOX9, COL2A1).
• Nerve growth factor (NGF) expression increased (1.8-fold), linked to neural sensitization and inflammatory pathways.
• Moderate loading induced a delayed chondrocyte apoptosis, distinct from immediate apoptosis seen with high-intensity stress.

Conclusions:

• Prolonged moderate mechanical loading promotes chondrocyte apoptosis via an NGF-mediated inflammatory pathway.
• Findings suggest early OA patients could benefit from limiting high-impact exercise to prevent cartilage damage.
• Provides mechanistic insights for guiding rehabilitation strategies in early osteoarthritis.