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  4. Effects of pharmacologic sclerostin inhibition or testosterone administration on soleus muscle atrophy in rodents after spinal cord injury

Effects of pharmacologic sclerostin inhibition or testosterone administration on soleus muscle atrophy in rodents after spinal cord injury

PLoS ONE, 2018 · DOI: https://doi.org/10.1371/journal.pone.0194440 · Published: March 26, 2018

Spinal Cord InjuryPharmacologyMusculoskeletal Medicine

Simple Explanation

This study investigates whether blocking sclerostin, a protein that inhibits bone formation, can prevent muscle loss after spinal cord injury (SCI) in rats. It compares the effects of a sclerostin antibody (Scl-Ab) to those of testosterone (TE), which is known to have muscle-building effects. The researchers found that Scl-Ab did not prevent muscle loss in the soleus muscle after SCI. This may be because the soleus muscle has low levels of the proteins that Scl-Ab needs to work. In comparison, TE partially prevented muscle loss. The study suggests that the effectiveness of TE in preventing muscle loss may depend on the type of muscle and its sensitivity to androgens (male hormones) because of the presence of androgen receptors. This work highlights that the anabolic actions of Scl-Ab occur relatively independently of muscle strain.

Study Duration
21 days
Participants
45 male Sprague-Dawley rats aged 5 months
Evidence Level
Not specified

Key Findings

  • 1
    Sclerostin antibody (Scl-Ab) did not prevent soleus muscle atrophy after spinal cord injury (SCI) in rats.
  • 2
    Testosterone enanthate (TE) partially prevented soleus atrophy and increased mass of the levator ani/bulbocavernosus (LABC) muscle complex after SCI.
  • 3
    The differing myotrophic responsiveness coincided with a 3-fold higher androgen receptor gene expression in LABC versus soleus.

Research Summary

This study investigated the effects of pharmacologic sclerostin inhibition and testosterone administration on muscle atrophy in rats after spinal cord injury (SCI). Sclerostin inhibition did not prevent soleus muscle atrophy. Testosterone administration partially prevented soleus atrophy and increased mass of the levator ani/bulbocavernosus (LABC) muscle complex. This indicates that androgen receptor expression may influence the myotrophic effects of testosterone in different muscles. The study suggests that mechanical stimuli may be necessary for Scl-Ab to promote anabolic response in skeletal muscle.

Practical Implications

Therapeutic Strategies

Targeting sclerostin inhibition alone may not be effective for preventing muscle atrophy after SCI, suggesting the need for combined approaches.

Personalized Medicine

Considering androgen receptor expression in specific muscles may optimize testosterone therapy for muscle preservation after SCI.

Further Research

Future studies should investigate the combination of sclerostin inhibition with mechanical loading to enhance muscle anabolic responses.

Study Limitations

  • 1
    The study did not demonstrate increased circulating sclerostin in the rodent model acutely after SCI, which contrasts with findings in humans.
  • 2
    The IH impactor model might be less severe than other SCI models.
  • 3
    The study only evaluated circulating sclerostin at day 21.

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