Osteopontin as a positive regulator in the osteoclastogenesis of arthritis

Taeko Ishii; Shiro Ohshima; Tetsushi Ishida; Toru Mima; Youichiro Tabunoki; Hideyuki Kobayashi; Masahiro Maeda; Toshimitsu Uede; Lucy Liaw; Naokazu Kinoshita; Ichiro Kawase; Yukihiko Saeki

doi:10.1016/j.bbrc.2004.02.124

Osteopontin as a positive regulator in the osteoclastogenesis of arthritis

Biochem Biophys Res Commun. 2004 Apr 9;316(3):809-15. doi: 10.1016/j.bbrc.2004.02.124.

Authors

Taeko Ishii¹, Shiro Ohshima, Tetsushi Ishida, Toru Mima, Youichiro Tabunoki, Hideyuki Kobayashi, Masahiro Maeda, Toshimitsu Uede, Lucy Liaw, Naokazu Kinoshita, Ichiro Kawase, Yukihiko Saeki

Affiliation

¹ Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.

PMID: 15033472
DOI: 10.1016/j.bbrc.2004.02.124

Abstract

We examined the role of osteopontin (OPN) in the osteoclastogenesis of arthritis using collagen-induced arthritis (CIA). Cells from arthritic joints of wild-type (OPN +/+) mice spontaneously developed bone-resorbing osteoclast-like cells (OCLs). The cultured cells showed an enhanced expression of receptor activator of nuclear factor kappaB ligand (RANKL) and a decreased expression of osteoprotegerin (OPG). The addition of OPG reduced the number of OCLs, indicating that the osteoclastogenesis depends on the RANK/RANKL/OPG system. The cells also produced OPN abundantly and anti-OPN neutralizing antibodies suppressed the development of OCLs. Moreover, the addition of OPN increased the expression of RANKL and augmented differentiation of OCLs from OPN-deficient (OPN -/-) cells. OPN, like the combination of 1alpha,25-dihydroxyvitamin D(3) and dexamethasone, also enhanced the RANKL expression and decreased OPG expression in a stromal cell line, ST2. These results suggest that OPN acts as a positive regulator in the osteoclastogenesis of arthritis through the RANK/RANKL/OPG system.

MeSH terms

Animals
Arthritis / etiology
Arthritis / metabolism*
Calcitriol / metabolism
Carrier Proteins / metabolism
Cell Differentiation
Cell Line
Cells, Cultured
Collagen / metabolism
Dexamethasone / pharmacology
Dose-Response Relationship, Drug
Gene Expression Regulation*
Glycoproteins / metabolism
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred DBA
Mice, Transgenic
Models, Genetic
Osteoclasts / metabolism
Osteopontin
Osteoprotegerin
RANK Ligand
RNA, Messenger / metabolism
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear / metabolism
Receptors, Tumor Necrosis Factor
Recombinant Proteins / chemistry
Reverse Transcriptase Polymerase Chain Reaction
Sialoglycoproteins / physiology*
Stromal Cells / cytology

Substances

Carrier Proteins
Glycoproteins
Membrane Glycoproteins
Osteoprotegerin
RANK Ligand
RNA, Messenger
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear
Receptors, Tumor Necrosis Factor
Recombinant Proteins
Sialoglycoproteins
Spp1 protein, mouse
Tnfrsf11a protein, mouse
Tnfrsf11b protein, mouse
Tnfsf11 protein, mouse
Osteopontin
Dexamethasone
Collagen
Calcitriol