Tissue-resident macrophages are present in virtually every organ of the body to execute a variety of vital functions and ensure tissue integrity and functionality. Single-cell RNA sequencing technology has recently helped us understand that macrophages are heterogeneous cells present in different phenotypes with distinct functions in tissues that are essentially dependent on microenvironment stimuli. While macrophages in a steady state maintain homeostasis, activated proinflammatory macrophages function as the first line of defense, combating invasive pathogens.

Anti-inflammatory macrophages maintain the balance of inflammatory and reparative processes. In musculoskeletal diseases, proinflammatory macrophages play a key role in the pathogenesis by initiating acute inflammation and tissue damage. The accumulation of senescent macrophages in tissues is associated with the development of a chronic inflammatory microenvironment, and excess production of proinflammatory cytokines and extracellular matrix components, leading to tissue remodeling and organ dysfunction. On the other hand, efferocytic macrophages play an essential role in the resolution of inflammation and initiating reparative processes in musculoskeletal tissues. Therefore, a better understanding of the macrophage subsets in tissues and the precise molecular mechanisms determining their functions should aid in the development of new therapeutic strategies for musculoskeletal disorders.

Musculoskeletal disorders represent a significant economic burden on individuals and medical services worldwide as they reduce mobility and productivity as well as the quality of life of individuals. Current therapeutic agents for the treatment of these disorders such as osteoarthritis and osteoporosis are not always effective in restoring the function of the affected tissues, and there is a need for alternative approaches to therapeutics. Mimicking the tactics of cells in our bodies that maintain or restore homeostasis is an attractive approach for therapeutics.

In this Research Topic, we welcome the submission of original research and review articles that cover, but are not limited to, the following topics:
• Role of macrophages in homeostatic, pathological, and reparative processes in musculoskeletal tissues.
• Macrophages secretome in the pathology of musculoskeletal tissues, such as bone, cartilage, and muscles.
• Molecular mechanisms underlining the regenerative ability of macrophages in bone, cartilage, muscle, and peripheral nerves.
• Biomaterial approach to cell reprogramming and differentiation that aid in restoring the homeostatic state of macrophages in musculoskeletal tissues.

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Frontiers in Immunology

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