Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice.
The aim of this study was to unravel the mechanisms by which interleukin (IL)-10, a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6 wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk of age. Interleukin-10 KO mice presented significant alveolar bone loss when compared with WT mice, and this was not associated with changes in leukocyte counts or bacterial load. The levels of expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, transforming growth factor-beta (TGF-beta), receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were similar between both strains, whereas a significant decrease of tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I collagen (COL-I) were expressed at similar levels in both strains, whereas the levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results demonstrate that the alveolar bone loss in the absence of IL-10 was associated with a reduced expression of osteoblast and osteocyte markers, an effect independent of microbial, inflammatory or bone-resorptive pathways.
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo (FOB/USP), Bauru, São Paulo, Brazil.
Marcela
M
Claudino
Thiago P
TP
Garlet
Cristina R B
CR
Cardoso
Gerson F
GF
de Assis
Rumio
R
Taga
Fernando Q
FQ
Cunha
João S
JS
Silva
Gustavo P
GP
Garlet
D016301:Alveolar Bone Loss / Q000378:metabolism*; D000539:Alveolar Process / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000096:biosynthesis; D003720:Densitometry; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D015870:Gene Expression; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis; D010011:Osteocytes / Q000378:metabolism*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D015415:Biomarkers; D024042:Collagen Type I; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D015675:Osteocalcin; D016753:Interleukin-10; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506232:Phex protein, mouse