Effect of monoclonal anti-human gp130 antibody (GPX7) on bone turnover in normal and ovariectomized rats.
We examined the effects of a monoclonal antihuman gp130 antibody (GPX7), which is known to inhibit interleukin-6 (IL-6) and leukemia inhibitory factor-mediated responses in human cells on the bone metabolism in normal and ovariectomized (OVX), 7-month-old, Wistar rats for 8 weeks. After confirming the cross-reactivity of the antibody in suppressing the IL-6-mediated proliferation of rat liver cells, GPX7 was injected once a week at doses of 1 (low dose) or 4 (high dose) mg/kg body weight (BW). In the lumbar body, bone mineral density values and the trabecular bone volume (BV/TV) were maintained in the GPX7 groups. The values of the trabecular osteoclast surface and number in the GPX7 high-dose group were significantly smaller than those in the OVX controls. The double-labeled surface and bone formation rates in the GPX7 high-dose group were significantly increased. In the proximal tibia, however, the bone mineral content and BV/ TV values in the GPX7 groups were smaller, but the trabecular thickness value in the GPX7 high-dose group was larger than in the OVX control. The single-labeled surface in the GPX7 high-dose group was significantly larger than that in the OVX control rats. Though the parameter values of trabecular osteoclasts were apparently smaller, the differences were not significant. 17-beta estradiol (0.125 mg/kg BW a week) administration prevented the bone loss by reducing the parameters of bone formation and resorption in both the lumbar and the proximal tibia. The antibody administration to the normal rats did not cause any significant changes in the parameters of bone mass and turnover. These data demonstrate that while GPX7 modulates the bone turnover after ovariectomy in rats, it does not compensate for the action of estrogen after ovariectomy in rats.
Nishida
S
S
Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Okimoto
N
N
Okazaki
Y
Y
Yamaguchi
A
A
Kumegawa
M
M
Yasukawa
K
K
Murayama
K
K
Nakamura
T
T
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D050822:Cytokine Receptor gp130; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D015675:Osteocalcin / Q000097:blood; D010052:Ovariectomy; D010758:Phosphorus / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C494199:IL6ST protein, human; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D015675:Osteocalcin; D050822:Cytokine Receptor gp130; D010758:Phosphorus; D004958:Estradiol; D000469:Alkaline Phosphatase; D002118:Calcium