Expression of osteopontin at sites of bone erosion in a murine experimental arthritis model of collagen-induced arthritis: possible involvement of osteopontin in bone destruction in arthritis.
OBJECTIVE
To investigate the involvement of osteopontin (OPN) in bone destruction in a murine experimental arthritis model of collagen-induced arthritis (CIA).


METHODS
The expression of OPN was examined at both the messenger RNA (mRNA) and protein levels in various arthritic lesions in mice with CIA by in situ hybridization and immunohistochemistry, respectively. In addition, the expression of alpha(v)beta3 integrin, a receptor for OPN, the ligation of which is thought to be essential for bone resorption by osteoclasts, was examined by immunohistochemistry. Plasma concentrations of OPN were measured at different time points in the course of CIA by enzyme-linked immunosorbent assay.


RESULTS
OPN mRNA was detected mainly at sites of bone erosion in arthritic lesions, where activated osteoclasts were present; OPN protein was also detected at sites of bone erosion. In the arthritic synovium, OPN was predominantly expressed in the synovial lining layer, but not in lymphoid aggregates. In addition, alpha(v)beta3 integrin was detected coincident with OPN at sites of bone erosion (bone-pannus junction). Plasma OPN levels were markedly elevated at the time points that corresponded to arthritis flares, and higher levels were maintained during the progression of arthritis.


CONCLUSIONS
OPN may mediate bone resorption by osteoclasts in arthritis through ligation with its receptor, alpha(v)beta3 integrin. OPN may be a useful therapeutic target molecule in the prevention of bone destruction in arthritis.
Ohshima
Shiro
S
Osaka University Medical School, Suita City, Osaka, Japan.
Kobayashi
Hideyuki
H
Yamaguchi
Norihiko
N
Nishioka
Katsuhiro
K
Umeshita-Sasai
Mitsuko
M
Mima
Toru
T
Nomura
Shintaro
S
Kon
Shigeyuki
S
Inobe
Manabu
M
Uede
Toshimitsu
T
Saeki
Yukihiko
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D051379:Mice; D010010:Osteoclasts / Q000473:pathology*; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis; D019030:Receptors, Vitronectin / Q000235:genetics; D012795:Sialoglycoproteins / Q000097:blood / Q000235:genetics*
D012333:RNA, Messenger; D019030:Receptors, Vitronectin; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin