RANKL in human periapical granuloma: possible involvement in periapical bone destruction.
OBJECTIVE
The cytokine receptor activator of nuclear factor kappaB-ligand (RANKL) has been involved in both the physiological and pathological regulation of osteoclast life span and bone metabolism. Periapical granuloma is a periradicular lesion characterized by periapical bone destruction. The aims of this study were to associate the RANKL mRNA levels to periapical granulomas using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to determine the specific cell involved in RANKL synthesis.


METHODS
In eight periapical granuloma and eight periodontal ligament samples from periodontally healthy volunteers, RANKL mRNA was detected by real-time RT-PCR. Expression of RANKL on infiltrate leukocytes was further investigated by flow cytometry in six periapical granulomas.


RESULTS
Receptor activator of nuclear factor kappaB-ligand mRNA levels were higher in periapical granulomas than in healthy periodontal ligament as its RANKL mRNA cycle threshold (Ct) and DeltaCt were significantly lower than that of controls (33.07 +/- 1.24 vs 36.96 +/- 1.69 and 11.58 +/- 3.02 vs 15.60 +/- 3.31, respectively). A 16.2-fold (2.0-131.6) higher RANKL gene expression was detected in the granulomas compared with the control tissues. We determined by flow cytometry that lymphocytes were the predominant leukocyte cells (53.31%), and monocytes and dendritic cells were the main RANKL synthesizers in granuloma lesions.


CONCLUSIONS
These data indicate that monocytes synthesized RANKL in periapical granulomas and suggest that RANKL is involved in bone loss associated with periapical lesions.
Vernal
R
R
Periodontal Biology Laboratory, Dentistry Faculty, University of Chile, Santiago, Chile. rvernal@uchile.cl
Dezerega
A
A
Dutzan
N
N
Chaparro
A
A
León
R
R
Chandía
S
S
Silva
A
A
Gamonal
J
J
D000293:Adolescent; D000328:Adult; D016301:Alveolar Bone Loss / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism; D010484:Periapical Granuloma / Q000378:metabolism*; D010513:Periodontal Ligament / Q000378:metabolism*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases