Interleukin (IL)-6, IL-11, leukemia inhibitory factor, and oncostatin M similarly induce osteoclast formation in cocultures of osteoblastic cells and bone marrow cells. These cytokines share a common signal transducer, gp130, which forms a receptor complex with the specific receptor for each cytokine. To investigate the role of gp130 in osteoclast development, we examined bone tissues in gp130-deficient and wild-type newborn mice of the ICR background. Soft x-ray radiographs and microfocus x-ray computed tomographs revealed that bone marrow cavities were present in tibiae and radii of both wild-type and gp130-deficient mice. Microfocus x-ray computed tomography and histological examination demonstrated a decrease in the amount of trabeculae at the metaphysial region in tibiae and radii of the gp130-deficient mice compared with the wild-type mice. The number ofosteoclasts in gp130-deficient mice was about double that in the wild-type mice. There were no apparent differences in the distributions of alkaline phosphatase-positive osteoblasts and the osteoid surface on the trabecular bone at the metaphysial region between the wild-type and gp130-deficient mice. The volume of mineralized trabecular bones was also decreased at mandibulae, accompanied by the increased number of osteoclasts in gp130-deficient mice compared with the wild-type and heterozygous mice. These results suggest that the formation of osteoclasts is not solely dependent on gp130 signaling, at least during fetal development. The osteoclastic bone resorption in gp130-deficient mice may be caused by the functional redundancy of bone-resorbing hormones and cytokines other than those of the IL-6 family.
To investigate the pathogenesis of accelerated bone formation in estrogen deficiency, diffusion chambers containing osteoblast-like cells isolated from newborn rat calvariae were transplanted into the peritoneal cavity of sham-operated (sham), ovariectomized (OVX) rats, and OVX rats with supplement of 17 beta-estradiol (OVX + E2). Bone formation in the diffusion chambers transplanted into OVX rats was more accelerated than that transplanted into sham rats and OVX + E2 rats. Osteoblast-like cells cultured with the sera isolated from OVX rats exhibited higher levels of the DNA content in the culture wells, alkaline phosphatase activity, messenger RNA expression for alkaline phosphatase and osteocalcin, calcium content in the cell layer, and formation of bone-like nodules than those exposed to the sera from sham rats and OVX + E2 rats. Antibody against IGF-I almost completely inhibited the increase in DNA contents induced by the sera isolated from OVX rats but partially inhibited alkaline phosphatase activity. Adding IGF-I to the sera isolated from sham rats increased the DNA content to the same extent as that induced by the supplement with the sera from OVX rats but did not increase alkaline phosphatase activity appreciably. Addition of various concentrations of 17 beta-estradiol, interleukin (IL)-1, and IL-6 to the sera isolated from sham rats did not increase the DNA content or alkaline phosphatase activity in the osteoblast-like cells. These results indicate that some systemic factor(s) other than IGF-I, IL-1, and IL-6 may be responsible for the stimulative effect on osteoblast differentiation in the pathogenesis of the accelerated bone formation induced by estrogen deficiency in rats.
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