Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model

Jianjun Ma, Jian Shen, Jeffrey P. Garrett, Cassandra A Lee, Zhongyu Li, Gamal A. Elsaidi, Andrew Ritting, Jeffrey Hick, Kim H. Tan, Thomas L. Smith, Beth P. Smith, L. Andrew Koman

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Neuromuscular junction destabilization following nerve injury contributes to irreversible functional impairment. Myogenic Regulatory Factors (MRF's) including myoblast determination factor (MyoD), MRF-4, Myogenin, and myogenic factors-5 (myf-5), and Growth-associated protein 43 KDa (GAP43) regulate gene expression of nicotinic acetylcholine receptor (nAChR) subunits (alpha, beta, delta, gamma, and epsilon). We hypothesized that nerve injury induces altered gene expression of MRF's, nAChRs, and GAP-43 in the skeletal muscle which destabilize neuromuscular junctions. The tibial nerve was transected in 42 juvenile male Sprague-Dawley rats. Denervated and contralateral control gastrocnemius m. mRNA for nAChR subunits, MRF's, and GAP-43 were determined by real time reverse transcription polymerase chain reaction (real time RT-PCR). After transection, muscle mass decreased for 1 year with a nadir of 75% at 3 months. Alpha, gamma, and epsilon subunit genes increased by 3 and peaked at 7 days before returning to control levels (P < 0.05). Beta subunits and GAP-43 tended to increase. Delta subunits peaked at 3 days returning to control levels by 30 days. By one month, most of the nAChR subunits had returned to control levels. Alpha, beta, gamma, and delta subunit expression remained significantly lower than control up to 1 year later (P < 0.05). MRF4, Myogenin, and MyoD expression paralleled that of alpha, gamma, and epsilon nAChR subunits (P < 0.05). Gene expression of nAChR alpha, gamma, delta and epsilon subunits was biphasic in the first month after nerve injury, similar to that of MRF's. nAChR subunits and MRF's may play a critical role in neuromuscular junction stability.

Original languageEnglish (US)
Pages (from-to)1498-1505
Number of pages8
JournalJournal of Orthopaedic Research
Volume25
Issue number11
DOIs
StatePublished - Nov 2007
Externally publishedYes

Keywords

  • Acetylcholine receptor
  • GAP-43
  • Myogenic regulatory factor
  • Nerve injury
  • Rat

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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    Ma, J., Shen, J., Garrett, J. P., Lee, C. A., Li, Z., Elsaidi, G. A., Ritting, A., Hick, J., Tan, K. H., Smith, T. L., Smith, B. P., & Koman, L. A. (2007). Gene expression of myogenic regulatory factors, nicotinic acetylcholine receptor subunits, and GAP-43 in skeletal muscle following denervation in a rat model. Journal of Orthopaedic Research, 25(11), 1498-1505. https://doi.org/10.1002/jor.20414