Local myogenic pulp-derived cell injection enhances craniofacial muscle regeneration in vivo

Orthod Craniofac Res. 2017 Feb;20(1):35-43. doi: 10.1111/ocr.12138.

Abstract

Objectives: To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5-aza-2'-deoxycytidine (5-Aza), and to evaluate the potent stimulatory effect of 5-Aza-treated pulp cell injection for craniofacial muscle regeneration in vivo.

Setting and sample population: Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18-22.1 years).

Material and methods: Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre-treatment of 5-Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)-labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)-induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice.

Results: Pre-treatment of 5-Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5-Aza pre-treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles.

Conclusion: The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo.

Keywords: 5-aza-2′-deoxycytidine; muscle injury; myogenesis; pulp cell; regeneration.

MeSH terms

  • Adolescent
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Bicuspid
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • DNA Methylation
  • Decitabine
  • Dental Pulp / cytology*
  • Humans
  • Masseter Muscle / physiology*
  • Muscle Development / physiology*
  • Muscle, Skeletal / physiology
  • Regeneration / drug effects
  • Regeneration / physiology*
  • Young Adult

Substances

  • Decitabine
  • Azacitidine