OPBSMusculoskeletalPathology
Must Know
- Skeletal muscle makes up over 40 percent of body mass.
- A motor unit is one motor neuron and the fibres it supplies, all of one fibre type.
- Repair is inflammation, proliferation and new matrix that stabilise the site, ending in regenerated muscle or scar.
- Regeneration restores tissue with histological, biochemical and mechanical properties close to native muscle.
- Volumetric muscle loss (VML) is tissue loss that exceeds the intrinsic regenerative capacity of muscle.
- Neutrophil myeloperoxidase damages membranes and triggers macrophage phagocytosis and efferocytosis.
- M1 macrophages (CD68 positive) arrive first, are phagocytic and release IL-6.
- M2 macrophages (CD163 and CD206 positive) are nonphagocytic and release IL-10, VEGF and TGF-β1.
- Imbalance between M1 and M2 macrophages favours fibrosis.
- Severe trauma creates an M1 dominated, TGF-β1 and IL-6 rich wound that permits fibrosis.
Fibre Types
| Type | Description |
|---|---|
| I | Slow twitch oxidative |
| IIa | Fast twitch fatigue resistant |
| IIb | Fast twitch fatigable |
Muscle Progenitor Cells
| Cell | Location | Marker |
|---|---|---|
| Satellite cell | Under the basal lamina of mature fibres, quiescent | Pax7 |
| Pericyte (perivascular cell) | Around microvessel endothelium | CD146, tissue nonspecific ALP |
| Mesenchymal stem cell | From the circulation | PDGFR-α, CD34, Sca-1 |
- Satellite cells are the most accepted muscle progenitor.
- Activated satellite cells proliferate, migrate, differentiate and fuse. A smaller fraction self-renews and returns to quiescence.
- Primary myogenesis fuses progenitors into multinucleated tubes. Secondary myogenesis grows them in length and width.
Regulators of Satellite Cells
| Factor | Effect |
|---|---|
| TGF-β | Drives fibroblast collagen and fibronectin, causing fibrosis. Low levels needed for regeneration |
| IGF-1 | Raises proliferation then differentiation and fusion. More muscle mass |
| HGF | Released from ECM early, activates satellite cells via c-met |
| FGF-2 | Stored in ECM, drives proliferation and suppresses differentiation |
| Laminin | Promotes differentiation |
| Fibronectin | Inhibits differentiation |
More on progenitor biology
- MSCs divide quickly then disappear after injury, first recruiting phagocytic macrophages then switching to anti-inflammatory signals.
- Prenatal pericytes contribute directly to the postnatal satellite cell pool.
- Satellite cells sit near capillaries (endocrine signals) and fibroblasts and immune cells (paracrine signals).
- Dystrophic muscle holds more collagen because of raised TGF-β.
- Muscular dystrophy causes repeated breakdown and regeneration with constant macrophage turnover and slowly building fibrosis.
Atrophy
| Feature | Denervation | Disuse | Ageing |
|---|---|---|---|
| Neuromuscular junction | Lost | Intact | Slowly degenerates |
| Satellite cells | Surge in first 2 months, then exhausted | Fall with prolonged disuse, regenerative capacity kept on reloading | Fall, especially past about 50 years |
| Other | Capillary loss 90 percent by 18 months | Reloading injury risk | Shift to slow type I fibres |
- Atrophy follows when catabolic protein breakdown exceeds anabolic synthesis.
- Early denervation disrupts Z-lines and loses actin and myosin. Capillary density falls after the first week.
- Distal axons undergo Wallerian degeneration once survival signals such as NMNAT are lost.
- Denervation activates NF-κB and the ubiquitin-proteasome pathway, releasing TNF-α and interleukins.
- Denervated membrane gains Na and Ca, loses K, and becomes more permeable to Na.
- Reinnervation after about 18 months gives little recovery of contraction or volume.
- Late denervated muscle is replaced by noncontractile connective tissue.
- Bed rest for 2 weeks cost 8 percent of mass and 6 percent of force.
- Immobilisation for 5 weeks cost 16 percent of mass and 18 percent of force.
- Ageing muscle loses type II alpha motor neurons. Type I neurons expand, giving more slow oxidative fibres.
- Aged muscle gains collagen I and loses laminin, proteoglycans and collagen IV, reducing satellite cell self-renewal.
- Old satellite cells regenerate normally when placed in young animals, so the environment drives decline.
More on denervation detail
- Connexins 39, 43 and 45 and pannexin channels increase in denervated membrane. Loss of connexin 43 and 45 reduced atrophy.
- Early in Wallerian degeneration axons still generate miniature end plate potentials.
- Damaged axons release factors that sensitise muscle to acetylcholine.
- SARM1 and PHR1 are also named in axonal breakdown signalling.
- Age-related muscle loss starts around 50 years and mirrors denervation, shown by matching myogenin and acetylcholine receptor RNA changes.
Clinical Muscle Injury
- Strains are tears from excessive stretch during contraction. First degree minor, third degree complete belly disruption.
- Almost all contusions and strains are treated with relative immobilisation, ice, rest and compression.
- Cryotherapy reduces intramuscular bleeding and inflammation.
- Gentle passive motion starts after 3 to 7 days. Early active motion worsens injury and increases scar.
- Complications include scar, myositis ossificans and reinjury.
- Complete lacerations retract and nerve fibres cannot cross the scar, leaving distal muscle denervated.
- Muscle holds sutures poorly. Grasping sutures through epimysium give the best hold.
- Repaired muscle is immobilised for 3 weeks before gentle motion.
- VML is treated by pedicled latissimus dorsi or free gracilis transfer, or tendon transfer.
- Tendon transfer needs an expendable donor of similar strength and excursion, straight line of pull and synergy.
- FCR to finger extensors is synergistic because wrist flexion pairs with finger extension.
- Donor resting tension is set to optimise myofilament overlap, based on the Blix curve.
- Muscle slide shifts the arc of motion but does not increase net range or force.
- Chronic denervation leaves too few axons. Motor units enlarge, but surviving fibres are small and weak.
More on tissue engineering for VML
- Strategies use a biological (decellularised) or synthetic scaffold, alone or with cells or growth factors.
- Scaffolds give neofibres only within a few millimetres of native tissue.
- Porcine small intestinal submucosa in human leg VML gave muscle islands with fibrosis dominating.
- Autologous muscle grafts for VML have functional recovery rates as low as 8 percent.
Exam Traps
- Satellite cells are marked by Pax7 and sit beneath the basal lamina, not outside it.
- HGF activates satellite cells through the c-met receptor.
- Fibronectin inhibits myogenic differentiation. Laminin promotes it.
- Disuse atrophy keeps neuromuscular junctions intact.
- Ageing shifts muscle towards slow type I fibres.
- Early active motion after a strain increases scar. Gentle passive motion is used.
Related pages. Muscle Tears and Ruptures
Source
McClure MJ, Christ GJ, Isaacs JE. Skeletal Muscle Repair and Regeneration. In. Aaron RK, editor. Orthopaedic Basic Science. Foundations of Clinical Practice. 5th ed. Philadelphia, Wolters Kluwer, 2021.
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Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 17 October 2026.