Diesel exhaust particles modulate bone remodeling and worsen osteoporosis: in vitro and in vivo investigations

Abstract

Air pollution poses significant risks to public health, with diesel exhaust particles (DEP) contributing to a variety of systemic effects, including potential impacts on bone metabolism. This study investigates DEP's osteogenic and bone toxic effects using both in vitro pre-osteoblast models and in vivo Zebrafish models under healthy and osteoporotic conditions. Pre-osteoblasts treated with DEP exhibited enhanced calcium deposition and upregulated osteogenic markers, including Runx2 and type I collagen, at 25–50 μg ml⁻¹ concentrations. Zebrafish larvae and adult models demonstrated similar concentration-dependent responses, with increased mineralization observed at lower DEP doses and reduced mineralization at higher concentrations (≥100 μg ml⁻¹). Notably, DEP exposure in osteoporotic Zebrafish consistently impaired bone regeneration and fracture healing, as evidenced by diminished calcium deposition, reduced alkaline phosphatase activity, and increased osteoclast activity. Mechanistically, DEP was shown to act through the aryl hydrocarbon receptor (AhR) pathway, disrupting the balance between osteoblast and osteoclast activity. At higher doses or under pathological conditions such as osteoporosis, DEP significantly impairs bone regeneration, delays fracture healing, and promotes bone resorption. The distinct responses elicited by these particles in healthy compared to osteoporotic bone highlight their dualistic nature and underscore the need for condition-specific investigation. This research underscores the importance of the risks associated with chronic DEP exposure in vulnerable populations. Future studies should focus on elucidating the molecular mechanisms underlying DEP's biphasic effects and exploring mitigation strategies for its adverse impacts on bone health.