Amelogenin is a negative regulator of osteoclastogenesis via downregulation of RANKL, M-CSF and fibronectin expression in osteoblasts.
Amelogenin is a novel enamel matrix protein. Knockout mice showed enhanced osteoclast formation and resorption of tooth cementum. This study investigated the effects of amelogenin on osteoclastogenesis. In co-cultures with calvaria osteoblasts and purified bone marrow cells, amelogenin inhibited osteoclastogenesis dramatically. Furthermore, amelogenin inhibited the expression of receptor activator of nuclear factor kappaB ligand (RANKL), macrophage-colony stimulating factor (M-CSF) and fibronectin in osteoblasts, while RANKL expression was induced by fibronectin and inhibited by treatment with fibronectin small interfering RNA. These results suggest that the inhibitory effects of amelogenin on osteoclastogenesis lead to downregulation of RANKL, M-CSF and fibronectin production in osteoblasts.
Nishiguchi
Miyuki
M
Division of Paediatric Dentistry, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Japan.
Yuasa
Kenji
K
Saito
Kan
K
Fukumoto
Emiko
E
Yamada
Aya
A
Hasegawa
Tomokazu
T
Yoshizaki
Keigo
K
Kamasaki
Yoko
Y
Nonaka
Kazuaki
K
Fujiwara
Taku
T
Fukumoto
Satoshi
S
D053523:Amelogenin / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D015536:Down-Regulation / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology*; D053245:RANK Ligand / Q000378:metabolism; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D012886:Skull / Q000166:cytology
D053523:Amelogenin; D005353:Fibronectins; D053245:RANK Ligand; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor