Exposure to polylactic acid microplastics during puberty increases the risk of skeletal dysplasia by disrupting arachidonic acid metabolism in osteoblasts

Biodegradable polylactic acid (PLA) plastic is considered to be an effective method to solve the global white pollution caused by petroleum-based plastics. Its wide application in disposable tableware and food packaging has led to the risk of human exposure to PLA microplastics (MPs), but its impact on bone health is unclear. Our study investigated the skeletal developmental toxicity of PLA-MPs at environmentally accessible concentrations in adolescent mice and its potential mechanism. Here we demonstrated that PLA-MPs treatment in adolescent mice showed significant skeletal developmental toxicity, manifested as shortened body length and slowed growth of femur and tibia. Further analysis found that PLA-MPs caused a diminution of epiphyseal plate thickness, a decrement in the count of bone trabeculae, damaged femoral microstructure, and inhibited femoral new bone formation. Notably, PLA-MPs enter osteoblasts and destroy their osteogenic differentiation, resulting in a dose-dependent damage that reduces the formation of calcium nodules. Transcriptome analysis further demonstrated that PLA-MPs exposure was associated with disrupted arachidonic acid metabolism, which may contribute to impaired osteoblast formation, especially Cyp2j5 gene and its downstream metabolite epoxyeicosatrienoic acids were significantly inhibited. Subsequent studies have indicated that Ophiopogonin D (Oph D) can activate Cyp2j5 signal to alleviate PLA-MPs-induced damaged osteoblast differentiation. Furthermore, alleviating impaired differentiation function of osteoblasts using Oph D can significantly improve the reduction of trabecular bone and bone microstructure damage caused by adolescent PLA-MPs exposure. This study not only identifies a potential mechanistic association between PLA-MPs exposure and poor bone development, but also emphasizes the need for targeted interventions to protect bone health in adolescent children and the broader impact on environmental and public health policies.