Extensive mononuclear infiltration and myogenesis characterize recovery of dysferlin-null skeletal muscle from contraction-induced injuries.

Abstract

We studied the response of dysferlin-null and control skeletal muscle to large- and small-strain injuries to the ankle dorsiflexors in mice. We measured contractile torque and counted fibers retaining 10-kDa fluorescein dextran, necrotic fibers, macrophages, and fibers with central nuclei and expressing developmental myosin heavy chain to assess contractile function, membrane resealing, necrosis, inflammation, and myogenesis. We also studied recovery after blunting myogenesis with X-irradiation. We report that dysferlin-null myofibers retain 10-kDa dextran for 3 days after large-strain injury but are lost thereafter, following necrosis and inflammation. Recovery of dysferlin-null muscle requires myogenesis, which delays the return of contractile function compared with controls, which recover from large-strain injury by repairing damaged myofibers without significant inflammation, necrosis, or myogenesis. Recovery of control and dysferlin-null muscles from small-strain injury involved inflammation and necrosis followed by myogenesis, all of which were more pronounced in the dysferlin-null muscles, which recovered more slowly. Both control and dysferlin-null muscles also retained 10-kDa dextran for 3 days after small-strain injury. We conclude that dysferlin-null myofibers can survive contraction-induced injury for at least 3 days but are subsequently eliminated by necrosis and inflammation. Myogenesis to replace lost fibers does not appear to be significantly compromised in dysferlin-null mice.

• Authors: Joseph A Roche, Richard M Lovering, Renuka Roche, Lisa W Ru, Patrick W Reed, Robert J Bloch
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 298 Issue 2 Pg. C298-312 (Feb 2010) ISSN: 1522-1563 [Electronic] United States
• PMID: 19923419 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dextrans
• Dysf protein, mouse
• Dysferlin
• Fluoresceins
• Membrane Proteins
• fluorescein-dextran

Topics

• Animals
• Cumulative Trauma Disorders (genetics, metabolism, pathology, physiopathology)
• Dextrans (metabolism)
• Disease Models, Animal
• Dysferlin
• Fluoresceins (metabolism)
• Inflammation (genetics, metabolism, pathology, physiopathology)
• Macrophages (metabolism, pathology)
• Male
• Membrane Proteins (deficiency, genetics)
• Mice
• Mice, Knockout
• Muscle Contraction
• Muscle Development (radiation effects)
• Muscle Fibers, Skeletal (metabolism, pathology)
• Muscle, Skeletal (metabolism, pathology, physiopathology, radiation effects)
• Muscular Dystrophies, Limb-Girdle (genetics, metabolism, pathology, physiopathology)
• Necrosis
• Recovery of Function
• Time Factors
• Torque