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Engineering Skeletal Muscle Tissues from Murine Myoblast Progenitor Cells and Application of Electrical Stimulation
Published on: March 19, 2013
Abstract:
The subcutaneous injection of mast cell degranulators in the mouse is followed by calcification of fibres of the Panniculus Carnosus muscle. This reaction is seen in damaged fibres adjacent to a central zone of complete necrosis. Calcification of muscle fibres is also seen after the injection of KMnO4 but this uniformly affects the fibres at the site of reaction. Quantitative studies of the latter model and qualitative studies of the former show that treatments with the diphosphonates EHDP and Cl2MDP do not influence the calcific responses. It is suggested that the inducing chemicals interact with the muscle fibre membrane causing membrane dysfunction and a resultant influx of calcium ions. It has been proposed that this is a pathogenetic mechanism in various myopathies and that prevention of net calcium ion influx might form a basis for treatment. In this context, the results of the present experiments suggest that the diphosphonates would be unlikely to efficacious in this regard.
Insights
Diphosphonates EHDP and Cl2MDP did not prevent muscle fiber calcification in mouse models. This suggests these compounds are unlikely to be effective treatments for myopathies involving calcium influx.
Area of Science:
- Muscle physiology
- Pathology
- Pharmacology
Background:
- Subcutaneous injection of mast cell degranulators or KMnO4 in mice induces calcification of Panniculus Carnosus muscle fibers.
- This calcification occurs in damaged fibers near necrosis or uniformly at the reaction site, respectively.
- Calcium influx into muscle fibers is a proposed mechanism in various myopathies.
Purpose of the Study:
- To investigate the effect of diphosphonates (EHDP and Cl2MDP) on chemically induced muscle fiber calcification in mice.
- To evaluate the potential of diphosphonates as a therapeutic strategy for myopathies characterized by calcium influx.
Main Methods:
- Subcutaneous injections of mast cell degranulators and KMnO4 were administered to mice.
- Muscle tissue was analyzed qualitatively and quantitatively following injections.
- The influence of EHDP and Cl2MDP treatments on calcific responses was assessed.
Main Results:
- Neither EHDP nor Cl2MDP treatments affected the calcification of muscle fibers induced by either agent.
- The study observed distinct patterns of calcification depending on the inducing chemical (mast cell degranulators vs. KMnO4).
Conclusions:
- The tested diphosphonates are unlikely to be efficacious in preventing muscle fiber calcification.
- The findings suggest that diphosphonates may not be suitable for treating myopathies where muscle fiber calcification is driven by calcium influx.
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