From inflammation to bone formation: the intricate role of neutrophils in skeletal muscle injury and traumatic heterotopic ossification

Abstract

Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-β signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO. Skeletal muscle, the body’s most common tissue, often gets injured and lacks highly effective treatments. This review investigates the complex relationship between skeletal muscle and neutrophils during injury and healing. Researchers study how neutrophils can both worsen muscle damage and assist in tissue repair. It looks at how neutrophil activity affects muscle repair, explaining the processes of inflammation, tissue regeneration, and the factors causing heterotopic ossification. It also emphasizes the significance of controlling neutrophil activity for effective muscle healing and avoiding complications. Key findings show that neutrophils are crucial in both harming and repairing skeletal muscle. Overactive neutrophils can cause extended inflammation, hindering the healing process, while controlled activity aids tissue regeneration. The researchers suggest that focusing on neutrophil activity could be a promising method for treating muscle injuries and preventing heterotopic ossification. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.