Prof Roberto Bottinelli
Department of Molecular Medicine
University of Pavia
Pavia, Italy

Mononuclear resident cells and skeletal muscle homeostasis in disuse: an overview.

Roberto Bottinelli¹, Maira Rossi^{1, 2}, Simone Porcelli¹, Cristiana Sazzi¹, Lorenza Brocca¹, Lorenzo Puri², Maria Antonietta Pellegrino¹

¹Department of Molecular Medicine University of Pavia, Italy;
²Development, Ageing and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA

So far, most studies aiming to clarify the mechanisms underlying muscle deterioration following disuse have understandably focused on muscle fibers and intracellular pathways controlling muscle mass, metabolism, and redox balance. However, a clear and comprehensive explanation of why loss of muscle mass and force occurs is still lacking. Recently, it has been understood that, although satellite cells are the stem cells which do repair and regenerate skeletal muscle fibers, other resident mononuclear cell populations (i.e., Fibro-Adipogenic Progenitors (FAPs), endothelial cells, immune cells, pericytes, tenocytes, glial cells, and Schwann cells) could play important roles not only in regeneration, but also in normal muscle homeostasis in conditions such as disuse and ageing (1). Among such cells, FAPs attracted most attention so far as a pivotal cell type that coordinates the activity of other muscle resident cell types, in response to homeostatic perturbations, via heterotypic interactions (5). While originally identified as interstitial muscle resident cells endowed with an inducible lineage bipotency, supporting either skeletal muscle regeneration or fibro-adipogenic degeneration (2, 4), subsequent studies have revealed a further functional heterogeneity. In particular, a growing amount of evidence is pointing to FAPs as mediators of muscle atrophy in response to denervation and ageing, possibly through interactions with neuromuscular junctions (NMJs) and NMJ-associated glial cells (3).

The potential role of FAPS cells and other mononuclear cell populations in normal muscle homeostasis and in disuse will be discussed.

References:

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