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Scleraxis and Fibroblast Specific Protein‐1 Identify Fibroblast Cells in Skeletal Muscle Tissue

Fibroblasts are thought to play an important role in the production and maintenance of the extracellular matrix (ECM) of skeletal muscle, but very few markers are known to identify fibroblasts in the cellular milieu of skeletal muscle ECM. Scleraxis (Scx) is a bHLH transcription factor that is critical for limb tendon development, and is a marker for fibroblasts from tendon. Fibroblast specific protein (FSP‐1), also known as S100A4, plays a role in cell motility and proliferation and has been used to identify fibroblasts in tissues from the liver, kidney, lung and heart. To identify markers for fibroblasts in skeletal muscle ECM, we tested the hypotheses that (i) Scx and FSP‐1 are expressed in fibroblast cells in mouse EDL muscles, and (ii) that the number of Scx and FSP‐1 positive cells would increase following muscle injury. Using immunohistochemistry, we identified a population of cells in skeletal muscle ECM that co‐express Scx and FSP‐1. Following injury, there was a dramatic increase in the number of Scx/FSP‐1 positive cells in the muscle ECM. The Scx/FSP‐1 positive population of cells was distinct from the satellite cell (c‐met), macrophage (F4/80) and neutrophil (Ly6) populations of cells. The results from these studies indicate that Scx and FSP‐1 are useful markers for fibroblasts in skeletal muscle ECM and may serve as potential therapeutic targets for the prevention of fibrosis following skeletal muscle injury.