Altered fibroblast proliferation and apoptosis in diabetic gingival wounds.
Although it is known that diabetes impairs oral wound healing, relatively little is known about the cellular parameters affected, particularly in connective tissue. This study investigated the hypothesis that diabetes impairs connective tissue formation in healing gingiva, and that impaired healing is associated with factors that decrease fibroblast numbers. Full-thickness wounds were created in the palatal gingiva of type 1 and type 2 diabetic and normoglycemic mice. Five days after wounding, diabetic mice had less epithelial wound coverage, less new connective tissue formation, and reduced fibroblast density (p < 0.05). This occurred with increased numbers of caspase-3- and TUNEL-positive fibroblasts, decreased fibroblast proliferation, increased nuclear translocation of the pro-apoptotic transcription factor FOXO1, and increased numbers of polymorphonuclear leukocytes, all of which were significant (p < 0.05). The results suggest that diabetes may decrease fibroblast numbers through increased apoptosis and reduced proliferation, both of which may be mediated through increased activation of FOXO1.
Desta
T
T
Department of Periodontics, NJDS-UMDNJ, 110 Bergen Street, Newark, NJ 07101-1709, USA.
Li
J
J
Chino
T
T
Graves
D T
DT
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000032:analysis; D002452:Cell Count; D002467:Cell Nucleus / Q000648:ultrastructure; D049109:Cell Proliferation; D003238:Connective Tissue / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis; D005881:Gingiva / Q000473:pathology* / Q000503:physiopathology; D005890:Gingivectomy; D020287:In Situ Nick-End Labeling; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014945:Wound Healing / Q000502:physiology
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; C505409:Casp3 protein, mouse; D053148:Caspase 3