09/02/2023
Sehr lesenswerter Beitrag über Muskelverletzungen👍🏻
A schematic overview of different steps during muscle repair. 💪
👉 Muscle injuries can stem from a variety of events, including direct trauma (i.e., muscle lacerations, contusions, or strains) and indirect causes (i.e., ischemia or neurological dysfunction, https://pubmed.ncbi.nlm.nih.gov/7810797/, https://pubmed.ncbi.nlm.nih.gov/2205779/, https://pubmed.ncbi.nlm.nih.gov/12004029/, https://pubmed.ncbi.nlm.nih.gov/1897874/).
👉Muscle injury is one of the most common injuries in professional and recreational sports. In fact, muscle injuries constitute between 10 and 55 % of all injuries sustained by athletes, depending on the type of sport (https://pubmed.ncbi.nlm.nih.gov/3812867/).
Whereas relatively minor muscle injuries, such as strains, can heal completely without intervention, severe muscle injuries typically result in the formation of dense scar tissue that impairs muscle function and can lead to muscle contracture and chronic pain. Injured muscle undergoes a sequential cycle of healing phases.
👉Skeletal muscle tissue comprises multiple cell types and compartments, including multinucleated myofibers, blood vessels, and neuromuscular junctions. Upon injury, this tissue recruits several cell types (represented in the figure) to repair myofibers.
1⃣ The starting phase of muscle regeneration, also known as a proinflammatory response, is characterized by the infiltration of immune cells that will clear the damaged fibers from the injured site. During the first phase, neutrophils (https://pubmed.ncbi.nlm.nih.gov/16101533/, https://pubmed.ncbi.nlm.nih.gov/17273473/, https://pubmed.ncbi.nlm.nih.gov/18784335/, https://pubmed.ncbi.nlm.nih.gov/11138776/, https://pubmed.ncbi.nlm.nih.gov/11138776/) and proinflammatory macrophages (also known as M1) are required to clean the muscle cell debris and participate in the recruitment and activation of other cell types (https://pubmed.ncbi.nlm.nih.gov/28555751/, https://pubmed.ncbi.nlm.nih.gov/20219869/).
2⃣ During the second stage, multiple cell types proliferate, including muscle stem cells (MuSC), also known as satellite cells . Other immune cells, such as regulatory T cells (known as Treg, https://pubmed.ncbi.nlm.nih.gov/24315098/) and eosinophils, also infiltrate the regenerating muscle after injury.
Eosinophils stimulate fibro-adipogenic progenitors (FAPs, a multipotent progenitor population resident in skeletal muscle) expansion by forming a transitional niche favorable to clear necrotic debris and prevent FAPs differentiation into adipocytes (https://pubmed.ncbi.nlm.nih.gov/23582327/).
In order to repair the damaged muscle, MuSC becomes activated, differentiate, and fuse to give rise to multinucleated myotubes. During this time, M1 macrophages are replaced by anti-inflammatory macrophages (also known as M2), which allows the restoration of the tissue.
They express anti-inflammatory markers, several extracellular matrix -related genes, and growth factors (such as TGF-ß) and contribute to the remodeling of the MuSC niche.
While M1 macrophages promote MuSC proliferation and prevent their premature differentiation, M2 macrophages boost MuSC commitment and formation of mature myotubes (https://pubmed.ncbi.nlm.nih.gov/29305000/, https://pubmed.ncbi.nlm.nih.gov/17485518/, https://pubmed.ncbi.nlm.nih.gov/32362490/, https://pubmed.ncbi.nlm.nih.gov/23169615/).
3⃣ New fibers are thus formed and grow during the last phase, named the restorative phase. MuSC repopulates their stem cell pool at this stage, the injured site is remodeled, and the tissue is recovered and can return to homeostasis.
Picture: https://pubmed.ncbi.nlm.nih.gov/35177651/