Periodontal ligament cells from insulin-dependent diabetics exhibit altered alkaline phosphatase activity in response to growth factors.
BACKGROUND
Insulin-dependent or Type 1 diabetes mellitus (IDDM) has been associated with an increased severity of periodontal disease. Because periodontal ligament (PDL) cells play a significant role in maintenance and regeneration of mineralized tissue, the success of procedures, such as guided tissue regeneration, is directly related to the ability of these cells to augment mineralized tissue. The objective of this study was to examine the ability of PDL cells from long-standing IDDM patients to form mineralized tissue and to determine whether these cells would exhibit altered responses to exogenously added growth factors.


METHODS
PDL cells were isolated from 4 patients with IDDM treated with insulin for at least 5 years and from systemically healthy donors. The cell isolates were tested for their ability to form mineralized nodules in vitro and to express alterations in alkaline phosphatase activity in response to exogenously added growth factors (transforming growth factor-beta (TGF-beta), platelet-derived growth factor-BB (PDGF-BB), and insulin-like growth factor-1 (IGF-1). Alkaline phosphatase activity was determined spectrophotometrically.


RESULTS
Although all PDL cell isolates formed mineralized nodules in vitro, PDL cells from diabetics formed mineralized nodules more slowly than did the controls. Alkaline phosphatase activity was not altered by exposure of diabetic PDL cells to TGF-beta for 9 days. In contrast, non-diabetic isolates exhibited increased levels of activity with increasing concentrations, from 0.5 to 1.0 ng/ml. Alkaline phosphatase activity was significantly higher in non-diabetic, but not in diabetic, cell isolates exposed to TGF-beta at 1.0 ng/ml, when compared to non-treated controls. Diabetic cell isolates exhibited significantly lower alkaline phosphatase activity than the non-diabetic isolates when exposed to either TGF-beta, PDGF-BB, IGF-1 or a combination of PDGF-BB and IGF-1.


CONCLUSIONS
These results suggest that the populations of PDL cells in insulin-dependent diabetics may be altered in their ability to form mineralized tissue and to respond to growth factors, functions affecting the maintenance and regeneration of the periodontium.
Hobbs
H C
HC
Department of Stomatology, School of Dentistry, University of California San Francisco, 94143-0650, USA.
Rowe
D J
DJ
Johnson
P W
PW
D000328:Adult; D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D000077214:Becaplermin; D002113:Calcification, Physiologic / Q000502:physiology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D013053:Spectrophotometry; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase