Flashcards in Lecture 28 - Muscle regeneration Deck (19):
The first event, following injury, is muscle _______and ________, which occurs within the first minutes and continues for up to ____to ____weeks after injury. Muscle regeneration begins _______________________ and peaks at about ____days post-injury. Fibrosis usually occurs at ___ ____ post-injury and increases over time for up to ___ weeks post-injury
The first event, following injury, is muscle degeneration and inflammation, which occurs within the first minutes and continues for up to one to two weeks after injury. Muscle regeneration begins in the first week post-injury and peaks at about 14 days post-injury. Fibrosis usually occurs at two weeks post-injury and increases over time for up to four weeks post-injury
What are the events leading to muscle fibre degeneration?
autolysis - activaiton of intracellular degradative enzymes (proteases and phospholipases)
an inflammatory response
- commmitment of phagocytic inflammatory cells
- localised neutrophils (realease degradative enzymes, destroy debris, incease vascular permeability)
- stimulate monocyte accumulation and satellite cells
- critical for initiating muscle fibre repair
- accumulated macrophages
What affects the usefulness of inflammation?
affected by viability of local vasculature
inflammatory response is critical for msucle fibre regeneration
too little, too much, too short or too long inflammation can all interfere with optimal regeneration
True or false
Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury
Myoblasts derived from the satellite cells fuse together to form...
myotubes with a maturity gradient
regenerated mscule fibre, with a new satellite cell and centrally located myonuclei
_______enables the new fibre to grow and mature and replaces the damaged portion of the fibre
Where possible regeneration is guided by extracellular structures
if the basal lamina is damaged...
myotube formation is impaired
e.g with a crushed limb, lacerations etc...
What is the concept of a ''maturity gradient''?
myotube formation/fibre maturation follows a maturity gradient
most advanced at surviving fibre stumps, less mature at centre of injury
internal re-organisation and MPS forms new fibres
maturation of protein isoforms
synthesis of new basal lamina
note: central nucleation during myotube formation as sign of early regeneration
Kinetics and amplitude of each regenerative phase may vary depending on:
extent of injury, the number of cells to replace
the muscle injured
the animal model
- species differences
- metabolic rate
differential expression of transcription factors, myogenic regulatory factors and growth factors
- ongoing injury/re-injury
- vascular supply
- inflammatory signature
- host (systemic) environment (young vs. Old)
- Neural function
- genetic influences
Chronological age alone is not a factor that limits the...
intrinsic ability of a msucle to regenerate
What is poor regeneration of muscle in old animals a function of?
the environment for regeneration provided by the old host
With ageing there is reduced:
physical activity (exercise)
trophic support: growth hormone (GH) and growth factors (e.g FGF, IGF)
True or False
shared circulation restored satellite cell activity in aged mice
circulating factors are important in muscle regeneration, not just factors intrinsic to muscle
Deficiency in _______ with increasing age contributes to the poor regeneration of muscles in old animals
True or false
Newly regenerated fibres in msucle of young and old animals are less resistant to injury
they are more resistant
maintenance of newly regenerated fibres by conditioning may prevent inadvertent damage, particularly in muscle of elderly people
What are changes in type of Myosin heavy chain folloing injury of a rat (soleus) slow twitch muscle?
less type 1 MyHC and more Type 11a fibres
How can growth factors enhance muscle repair after injury?
GF (e.g IGF-1) can improve muscle regeneration, but the post-injury healing process remains incomplete
the use of anti-fibrotic agnets that antagonise the effect of TGF-beta1 can prevent fibrosis and improve muscle healing and recovery
optimal muscle recovery may require the use of novel technologies, such as:
cell therapy, gene therapy and tissue engineering.
needed to achieve high levels and long-term persistence of these GFs and cytokines within the muscle