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. 1987 Jan 1;104(1):109–120. doi: 10.1083/jcb.104.1.109

Cell accumulation in the junctional region of denervated muscle

PMCID: PMC2117033  PMID: 3491825

Abstract

If skeletal muscles are denervated, the number of mononucleated cells in the connective tissue between muscle fibers increases. Since interstitial cells might remodel extracellular matrix, and since extracellular matrix in nerve and muscle plays a direct role in reinnervation of the sites of the original neuromuscular junctions, we sought to determine whether interstitial cell accumulation differs between junctional and extrajunctional regions of denervated muscle. We found in muscles from frog and rat that the increase in interstitial cell number was severalfold (14-fold for frog, sevenfold for rat) greater in the vicinity of junctional sites than in extrajunctional regions. Characteristics of the response at the junctional sites of frog muscles are as follows. During chronic denervation, the accumulation of interstitial cells begins within 1 wk and it is maximal by 3 wk. Reinnervation 1-2 wk after nerve damage prevents the maximal accumulation. Processes of the cells form a multilayered veil around muscle fibers but make little, if any, contact with the muscle cell or its basal lamina sheath. The results of additional experiments indicate that the accumulated cells do not originate from terminal Schwann cells or from muscle satellite cells. Most likely the cells are derived from fibroblasts that normally occupy the space between muscle fibers and are known to make and degrade extracellular matrix components.

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Selected References

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  1. Abercrombie M., Johnson M. L. Quantitative histology of Wallerian degeneration: I. Nuclear population in rabbit sciatic nerve. J Anat. 1946 Jan;80(Pt 1):37–50. [PMC free article] [PubMed] [Google Scholar]
  2. Akers R. M., Mosher D. F., Lilien J. E. Promotion of retinal neurite outgrowth by substratum-bound fibronectin. Dev Biol. 1981 Aug;86(1):179–188. doi: 10.1016/0012-1606(81)90328-6. [DOI] [PubMed] [Google Scholar]
  3. Anglister L., McMahan U. J. Basal lamina directs acetylcholinesterase accumulation at synaptic sites in regenerating muscle. J Cell Biol. 1985 Sep;101(3):735–743. doi: 10.1083/jcb.101.3.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BIRKS R., KATZ B., MILEDI R. Physiological and structural changes at the amphibian myoneural junction, in the course of nerve degeneration. J Physiol. 1960 Jan;150:145–168. doi: 10.1113/jphysiol.1960.sp006379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BRANWOOD A. W. THE FIBROBLAST. Int Rev Connect Tissue Res. 1963;1:1–28. doi: 10.1016/b978-1-4831-6755-8.50006-1. [DOI] [PubMed] [Google Scholar]
  6. Bradley W. G., Asbury A. K. Duration of synthesis phase in neuilemma cells in mouse sciatic nerve during degeneration. Exp Neurol. 1970 Feb;26(2):275–282. doi: 10.1016/0014-4886(70)90125-1. [DOI] [PubMed] [Google Scholar]
  7. Burden S. J., Sargent P. B., McMahan U. J. Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve. J Cell Biol. 1979 Aug;82(2):412–425. doi: 10.1083/jcb.82.2.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cornbrooks C. J., Carey D. J., McDonald J. A., Timpl R., Bunge R. P. In vivo and in vitro observations on laminin production by Schwann cells. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3850–3854. doi: 10.1073/pnas.80.12.3850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Covault J., Sanes J. R. Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4544–4548. doi: 10.1073/pnas.82.13.4544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fallon J. R., Nitkin R. M., Reist N. E., Wallace B. G., McMahan U. J. Acetylcholine receptor-aggregating factor is similar to molecules concentrated at neuromuscular junctions. Nature. 1985 Jun 13;315(6020):571–574. doi: 10.1038/315571a0. [DOI] [PubMed] [Google Scholar]
  11. Heathcote R. D., Sargent P. B. The genesis and differentiation of neurons in a frog parasympathetic ganglion. Dev Biol. 1984 Sep;105(1):102–114. doi: 10.1016/0012-1606(84)90265-3. [DOI] [PubMed] [Google Scholar]
  12. Hess A., Rosner S. The satellite cell bud and myoblast in denervated mammalian muscle fibers. Am J Anat. 1970 Sep;129(1):21–39. doi: 10.1002/aja.1001290103. [DOI] [PubMed] [Google Scholar]
  13. Ide C., Tohyama K., Yokota R., Nitatori T., Onodera S. Schwann cell basal lamina and nerve regeneration. Brain Res. 1983 Dec 12;288(1-2):61–75. doi: 10.1016/0006-8993(83)90081-1. [DOI] [PubMed] [Google Scholar]
  14. Jansen J. K., Van Essen D. C. Re-innervation of rat skeleton muscle in the presence of alpha-bungarotoxin. J Physiol. 1975 Sep;250(3):651–667. doi: 10.1113/jphysiol.1975.sp011075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. KARNOVSKY M. J. THE LOCALIZATION OF CHOLINESTERASE ACTIVITY IN RAT CARDIAC MUSCLE BY ELECTRON MICROSCOPY. J Cell Biol. 1964 Nov;23:217–232. doi: 10.1083/jcb.23.2.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Konigsberg U. R., Lipton B. H., Konigsberg I. R. The regenerative response of single mature muscle fibers isolated in vitro. Dev Biol. 1975 Aug;45(2):260–275. doi: 10.1016/0012-1606(75)90065-2. [DOI] [PubMed] [Google Scholar]
  17. Lander A. D., Fujii D. K., Reichardt L. F. Laminin is associated with the "neurite outgrowth-promoting factors" found in conditioned media. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2183–2187. doi: 10.1073/pnas.82.7.2183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Letinsky M. S., Fischbeck K. H., McMahan U. J. Precision of reinnervation of original postsynaptic sites in frog muscle after a nerve crush. J Neurocytol. 1976 Dec;5(6):691–718. doi: 10.1007/BF01181582. [DOI] [PubMed] [Google Scholar]
  19. Lipton B. H. Collagen synthesis by normal and bromodeoxyuridine-modulated cells in myogenic culture. Dev Biol. 1977 Dec;61(2):153–165. doi: 10.1016/0012-1606(77)90288-3. [DOI] [PubMed] [Google Scholar]
  20. Lipton B. H., Schultz E. Developmental fate of skeletal muscle satellite cells. Science. 1979 Sep 21;205(4412):1292–1294. doi: 10.1126/science.472747. [DOI] [PubMed] [Google Scholar]
  21. MAURO A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961 Feb;9:493–495. doi: 10.1083/jcb.9.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Manthorpe M., Engvall E., Ruoslahti E., Longo F. M., Davis G. E., Varon S. Laminin promotes neuritic regeneration from cultured peripheral and central neurons. J Cell Biol. 1983 Dec;97(6):1882–1890. doi: 10.1083/jcb.97.6.1882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marshall L. M., Sanes J. R., McMahan U. J. Reinnervation of original synaptic sites on muscle fiber basement membrane after disruption of the muscle cells. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3073–3077. doi: 10.1073/pnas.74.7.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McGeachie J., Allbrook D. Cell proliferation in skeletal muscle following denervation or tenotomy. A series of autoradiographic studies. Cell Tissue Res. 1978 Oct 17;193(2):259–267. doi: 10.1007/BF00209039. [DOI] [PubMed] [Google Scholar]
  25. McMahan U. J., Slater C. R. The influence of basal lamina on the accumulation of acetylcholine receptors at synaptic sites in regenerating muscle. J Cell Biol. 1984 Apr;98(4):1453–1473. doi: 10.1083/jcb.98.4.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murray M. A., Robbins N. Cell proliferation in denervated muscle: identity and origin of dividing cells. Neuroscience. 1982 Jul;7(7):1823–1833. doi: 10.1016/0306-4522(82)90040-9. [DOI] [PubMed] [Google Scholar]
  27. Murray M. A., Robbins N. Cell proliferation in denervated muscle: time course, distribution and relation to disuse. Neuroscience. 1982 Jul;7(7):1817–1822. doi: 10.1016/0306-4522(82)90039-2. [DOI] [PubMed] [Google Scholar]
  28. Ontell M. Muscle satellite cells: a validated technique for light microscopic identification and a quantitative study of changes in their population following denervation. Anat Rec. 1974 Feb;178(2):211–227. doi: 10.1002/ar.1091780206. [DOI] [PubMed] [Google Scholar]
  29. Rieger F., Grumet M., Edelman G. M. N-CAM at the vertebrate neuromuscular junction. J Cell Biol. 1985 Jul;101(1):285–293. doi: 10.1083/jcb.101.1.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rogers S. L., Letourneau P. C., Palm S. L., McCarthy J., Furcht L. T. Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin. Dev Biol. 1983 Jul;98(1):212–220. doi: 10.1016/0012-1606(83)90350-0. [DOI] [PubMed] [Google Scholar]
  31. Ross R., Everett N. B., Tyler R. Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis. J Cell Biol. 1970 Mar;44(3):645–654. doi: 10.1083/jcb.44.3.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rutishauser U., Grumet M., Edelman G. M. Neural cell adhesion molecule mediates initial interactions between spinal cord neurons and muscle cells in culture. J Cell Biol. 1983 Jul;97(1):145–152. doi: 10.1083/jcb.97.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Salonen V., Lehto M., Kalimo M., Penttinen R., Aro H. Changes in intramuscular collagen and fibronectin in denervation atrophy. Muscle Nerve. 1985 Feb;8(2):125–131. doi: 10.1002/mus.880080208. [DOI] [PubMed] [Google Scholar]
  34. Salzer J. L., Bunge R. P. Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury. J Cell Biol. 1980 Mar;84(3):739–752. doi: 10.1083/jcb.84.3.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sanderson R. D., Fitch J. M., Linsenmayer T. R., Mayne R. Fibroblasts promote the formation of a continuous basal lamina during myogenesis in vitro. J Cell Biol. 1986 Mar;102(3):740–747. doi: 10.1083/jcb.102.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sanes J. R. Laminin, fibronectin, and collagen in synaptic and extrasynaptic portions of muscle fiber basement membrane. J Cell Biol. 1982 May;93(2):442–451. doi: 10.1083/jcb.93.2.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sanes J. R., Marshall L. M., McMahan U. J. Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. J Cell Biol. 1978 Jul;78(1):176–198. doi: 10.1083/jcb.78.1.176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sanes J. R., Schachner M., Covault J. Expression of several adhesive macromolecules (N-CAM, L1, J1, NILE, uvomorulin, laminin, fibronectin, and a heparan sulfate proteoglycan) in embryonic, adult, and denervated adult skeletal muscle. J Cell Biol. 1986 Feb;102(2):420–431. doi: 10.1083/jcb.102.2.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Smalheiser N. R., Crain S. M., Reid L. M. Laminin as a substrate for retinal axons in vitro. Brain Res. 1984 Jan;314(1):136–140. doi: 10.1016/0165-3806(84)90184-6. [DOI] [PubMed] [Google Scholar]
  40. Snow M. H. A quantitative ultrastructural analysis of satellite cells in denervated fast and slow muscles of the mouse. Anat Rec. 1983 Dec;207(4):593–604. doi: 10.1002/ar.1092070407. [DOI] [PubMed] [Google Scholar]
  41. THOMAS P. K. The connective tissue of peripheral nerve: an electron microscope study. J Anat. 1963 Jan;97:35–44. [PMC free article] [PubMed] [Google Scholar]
  42. Thomas G. A. Quantitative histology of Wallerian degeneration: II. Nuclear population in two nerves of different fibre spectrum. J Anat. 1948 Jul;82(Pt 3):135–145. [PMC free article] [PubMed] [Google Scholar]
  43. Walrond J. P., Reese T. S. Structure of axon terminals and active zones at synapses on lizard twitch and tonic muscle fibers. J Neurosci. 1985 May;5(5):1118–1131. doi: 10.1523/JNEUROSCI.05-05-01118.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zak R., Grove D., Rabinowitz M. DNA synthesis in the rat diaphragm as an early response to denervation. Am J Physiol. 1969 Mar;216(3):647–654. doi: 10.1152/ajplegacy.1969.216.3.647. [DOI] [PubMed] [Google Scholar]

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