The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.
METHODS
We injected two drugs that modify the epigenome, the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA), alone or in combination, into C57Bl/6 mice subjected to amputation through the mid-second phalanx of the third digit. Wound-site tissue was collected.


RESULTS
We observed increased staining of the stem cell markers Rex1 (Zfp42) and stem cell antigen-1 at digit amputation sites from drug-treated mice. Samples from 5-aza-dC plus TSA and TSA treated mice also showed increased proliferating cell nuclear antigen staining, a measure of cell proliferation. Drug treatments increased Msx1, but not Cyp26a1 or ALDH1a2 (RALDH2) mRNA.


CONCLUSIONS
5-aza-dC and TSA treatments stimulated cell proliferation at the amputation site, possibly via increased expression of genes involved in digit development and regeneration.
Wang
Gang
G
Department of Pharmacology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA. ljgudas@med.cornell.edu
Badylak
Stephen F
SF
Heber-Katz
Ellen
E
Braunhut
Susan J
SJ
Gudas
Lorraine J
LJ
D000671:Amputation, Surgical; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D005260:Female; D005552:Forelimb / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D013194:Staining and Labeling; D014034:Toes / Q000502:physiology*
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C012589:trichostatin A; D008780:Methyltransferases; D001374:Azacitidine