title: Decreased expression of p63, a regulator of epidermal stem cells, in the chronic laminitic equine hoof.
abstract: BACKGROUND
  Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis.
  
  
  OBJECTIVE
  To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis.
  
  
  METHODS
  Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 control horses. Tissues were analysed using histopathology, immunofluorescence microscopy and quantitative immunoblotting.
  
  
  RESULTS
  Hoof lamellae of laminitic horses had a lower frequency of p63 positive cells than control lamellae, particularly in the distal region. Quantitative immunoblotting confirmed reduced p63 expression in the laminitic distal lamellar region. The decreased p63 expression in laminitic epidermal lamellae was most apparent in the abaxial region adjacent to the hoof wall and highly associated with the formation of terminally differentiated, dysplastic and hyperkeratotic epidermis in this region, whereas lamellae from control horses maintained high p63 expression throughout the axial-abaxial axis.
  
  
  CONCLUSIONS
  Expression of p63 in equine skin resembles that reported in other species, including man and rodents, suggesting that p63 can serve as a marker for the proliferative potential of equine epidermal stem cells. p63 expression was significantly lower in the chronic laminitic hoof than in that of control horses, suggesting laminitic hoof epithelium has more limited proliferative potential with a shift towards differentiation. This may reflect reduced activity of epidermal stem cells in laminitic hoof. It is proposed that p63 contributes to the maintenance of hoof lamellae and that misregulation of p63 expression may lead to epidermal dysplasia during lamellar wedge formation.
  
  
  CONCLUSIONS
  This study suggests that loss of epidermal stem cells contributes to the pathogenesis of equine laminitis. Autologous transplantation of p63-positive epidermal stem cells from unaffected regions may have regenerative therapeutic potential for laminitic horses.
authors.affiliation: Laminitis Institute, Department of Clinical Studies/New Bolton Center, University of Pennsylvania School of Veterinary Medicine, PA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Carter
authors.forename: J B
authors.initials: JB
authors.lastname: Engiles
authors.forename: S O
authors.initials: SO
authors.lastname: Megee
authors.forename: M
authors.initials: M
authors.lastname: Senoo
authors.forename: H L
authors.initials: HL
authors.lastname: Galantino-Homer
mesh_terms: D000818:Animals; D002908:Chronic Disease; D005260:Female; D005534:Foot Diseases / Q000378:metabolism / Q000662:veterinary*; D005786:Gene Expression Regulation; D006724:Hoof and Claw / Q000378:metabolism*; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D007249:Inflammation / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D025521:Tumor Suppressor Proteins