Macrophage colony stimulating factor-induced macrophage differentiation influences myotube elongation.

BACKGROUND: Unaccustomed exercise, high-intensity dynamic sports activities, or the resumption of normal weight-bearing after a period of disuse can induce skeletal muscle injury, which activates an inflammatory response followed by muscle regeneration. Specific subsets of macrophages are involved in muscle regeneration. But the exact role of macrophage differentiation during muscle regeneration remains to be elucidated. OBJECTIVE: The objective of the study was to examine the effect of macrophage colony stimulating factor (M-CSF)-differentiated, lipopolysaccharides (LPS)-stimulated-macrophage-conditioned medium on muscle-cell proliferation, fusion, and elongation, which are key events during muscle regeneration and myogenesis. METHOD: Murine C2C12 myoblasts were cultured in conditioned medium obtained from PU5-1R macrophages that were (a) undifferentiated, unstimulated; (b) M-CSF-differentiated, unstimulated; (c) undifferentiated, LPS-stimulated; or (d) M-CSF-differentiated, LPS-stimulated. Myoblast proliferation ratio, nuclei number, and length were measured. RESULTS: C2C12 cells cultured in conditioned medium from M-CSF-differentiated, LPS-stimulated macrophages had significantly more nuclei and greater length than cells cultured in conditioned medium from undifferentiated, LPS-stimulated macrophages. Dilution and denaturization of the M-CSF-differentiated, LPS-stimulated-macrophage medium prevented a marked increase in C2C12 nuclei number and length. However, the C2C12 myoblast proliferation ratio was significantly greater in conditioned medium from undifferentiated, LPS-stimulated macrophages than in conditioned medium from M-CSF-differentiated, LPS-stimulated macrophages. CONCLUSIONS: M-CSF-differentiated, LPS-stimulated macrophages may influence myogenesis and the early and terminal stages of muscle regeneration. This knowledge may aid in developing therapies that will directly expedite muscle repair and lead to faster rehabilitation and reduced rehabilitation costs.

A rodent model to advance the field treatment of crush muscle injury during earthquakes and other natural disasters.

Approximately 170 earthquakes of 6.0 or higher magnitude occur annually worldwide. Victims often suffer crush muscle injuries involving impaired blood flow to the affected muscle and damage to the muscle fiber membrane. Current rescue efforts are directed toward preventing acute kidney injury (AKI), which develops upon extrication and muscle reperfusion. But field-usable, muscle-specific interventions may promote muscle regeneration and prevent or minimize the pathologic changes of reperfusion. Although current rodent crush injury models involve reperfusion upon removal of the crush stimulus, an analysis of their methodological aspects is needed to ensure adequate simulation of the earthquake-related crush injury. The objectives of this systematic review are to (a) describe rodent crush muscle injury models, (b) discuss the benefits and limitations of these models, and (c) offer a recommendation for animal models that would increase our understanding of muscle recovery processes after an earthquake-induced crush muscle injury. The most commonly used rodent model uses a clamping or pressing crush stimulus directly applied to murine hindlimb muscle. This model has increased our understanding of muscle regeneration but its open approach does not adequately represent the earthquake-related crush injury. The model we recommend for developing field-usable, muscle-specific interventions is a closed approach that involves a nonclamping crush stimulus. Findings from studies employing this recommended model may have greater relevance for developing interventions that lessen the earthquake's devastating impact on individual and community health and quality of life, especially in developing countries.