Mechanical Loading Prevents Bone Growth Impairment in TNF-Overexpressing Mice with Chronic Inflammation

Introduction: Mechanical loading has been shown to accelerate bone growth in healthy mice, but if this is the case also in growth suppressed animals with an inflammatory condition remains unexplored. To address this, we explored the potential for mechanical loading to stimulate longitudinal bone growth under conditions of chronic inflammation. Methods: A transgenic mouse model overexpressing human tumor necrosis factor (huTNFTg) was used to mimic chronic inflammation. Six-week-old animals were exposed to daily mechanical loading, applied laterally to the right knee joint, 5 times per week for 4 weeks while bone growth was monitored weekly. The contralateral side was sham-loaded and served as an internal control. At the endpoint, growth plate morphology was assessed. For mechanistic studies, fetal rat femur bones were cultured ex vivo with cytokines added for 12 days while mechanical loading was applied every 2-3 days. Results: Mechanical loading stimulated femur bone growth, not only in wild-type controls but also in huTNFTg mice. Growth plate morphometric analyses revealed reduced growth plate height and hypertrophic zone heights in huTNFTg mice, and mechanical loading was able to counteract these changes. Ex vivo studies in cultured femur bones showed that mechanical loading can partially prevent cytokine-induced bone growth suppression, suggesting that the effect is locally mediated, rather than systemically. Conclusions: Our in vivo and ex vivo data showed that mechanical loading locally stimulates bone growth even when exposed to inflammatory cytokines. These findings suggest that mechanical loading may have a beneficial role in regulating bone growth under chronic inflammatory conditions.