Alveolar bone loss in T helper 1/T helper 2 cytokine-deficient mice.
OBJECTIVE
The role of cytokines in bone loss is important in the context of periodontitis, where inflammation-induced bone destruction is a major manifestation. Numerous cytokines have been implicated as mediators of bone resorption. The purpose of this study was to observe the impact of targeted gene deletion of T helper 1 (Th1) and T helper 2 (Th2) cytokines on naturally occurring alveolar bone loss in genetically modified mice.


METHODS
Alveolar bone loss was measured histomorphometrically in interleukin-4, interleukin-10, interleukin-12p40, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) knockout mice at 6, 16 and 30 wk of age.


RESULTS
Both Th1 (interleukin-12p40, IFN-gamma, TNF) and Th2 (interleukin-10, interleukin-4) knockout mice exhibited significantly more alveolar bone loss than their respective wild-type control mice (p<0.001). Interleukin-10-/- and interleukin-12p40-/- mice exhibited a three-fold increase in alveolar bone loss at 30 wk of age, whereas bone loss in IFN-gamma-/-, TNF-/- and interleukin-4-/- mice was 1.5- to two-fold higher compared with wild-type control mice.


CONCLUSIONS
The results of the present study indicate that both Th1 and Th2 cytokines play an important role in maintaining alveolar bone homeostasis. The kinetics of alveolar bone loss seen in cytokine gene knockout mice indicates that bone loss is age dependent and late in onset.
Alayan
J
J
Oral Biology and Pathology, School of Dentistry, University of Queensland, Brisbane, Qld, Australia.
Ivanovski
S
S
Farah
C S
CS
D000367:Age Factors; D016301:Alveolar Bone Loss / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology; D007378:Interleukins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma