Osteopontin is associated with nuclear factor kappaB gene expression during tail-suspension-induced bone loss.
Osteoporosis due to unloading-induced bone loss is a critical issue in the modern aging society. Although the mechanisms underlying this phenomenon are largely unknown, osteopontin (OPN) is one of the critical mediators required for unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med, 193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried out microarray analyses on the genes expressed in the femoral bone marrow cells in wild type and OPN-/- mice. The removal of the mechanical load induced bone loss in wild type, but not in OPN-/- mice, as previously reported. Expression analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency blocked tail-suspension-induced expression of ten genes (group A). This observation was confirmed based on semi-quantitative RT-PCR analyses. On the other hand, expression of four genes (group B) was not altered by tail suspension in wild type but was enhanced in OPN-deficient mice. NF-kappaB p105 subunit gene (Nfkb1) was found in group A and Bax in group B. p53 gene expression was upregulated by tail suspension in wild type mice, but it was no longer observed in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress signaling upstream to the genes encoding apoptosis-related molecules, and its action is associated with alteration of the genes.
Ishijima
Muneaki
M
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10, Kanda-Surugadai 2-Chome, Chiyoda-Ku, Tokyo 101-0062, Japan.
Ezura
Yoichi
Y
Tsuji
Kunikazu
K
Rittling
Susan R
SR
Kurosawa
Hisashi
H
Denhardt
David T
DT
Emi
Mitsuru
M
Nifuji
Akira
A
Noda
Masaki
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001862:Bone Resorption / Q000139:chemically induced*; D015536:Down-Regulation / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics; D015870:Gene Expression; D019417:Hindlimb Suspension / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000172:deficiency / Q000378:metabolism*; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
D051766:Early Growth Response Protein 1; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D051028:bcl-2-Associated X Protein; D053495:Osteopontin; C073701:Nfkb1 protein, mouse