Kawasaki K, Gao Y H, Yokose S, Kaji Y, Nakamura T, Suda T, Yoshida K, Taga T, Kishimoto T, Kataoka H, Yuasa T, Norimatsu H, Yamaguchi A
Department of Oral Pathology, School of Dentistry, Showa University, Tokyo, Japan.
Endocrinology. 1997 Nov;138(11):4959-65. doi: 10.1210/endo.138.11.5534.
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.
白细胞介素（IL）-6、IL-11、白血病抑制因子和制瘤素M在成骨细胞与骨髓细胞的共培养体系中同样能诱导破骨细胞形成。这些细胞因子共享一个共同的信号转导子gp130，它与每种细胞因子的特异性受体形成受体复合物。为了研究gp130在破骨细胞发育中的作用，我们检测了ICR背景的gp130基因敲除新生小鼠和野生型新生小鼠的骨组织。软X线片和微焦点X线计算机断层扫描显示，野生型和gp130基因敲除小鼠的胫骨和桡骨中均存在骨髓腔。微焦点X线计算机断层扫描和组织学检查表明，与野生型小鼠相比，gp130基因敲除小鼠胫骨和桡骨干骺端区域的小梁数量减少。gp130基因敲除小鼠中的破骨细胞数量约为野生型小鼠的两倍。野生型和gp130基因敲除小鼠干骺端区域小梁骨上碱性磷酸酶阳性成骨细胞的分布和类骨质表面没有明显差异。与野生型和杂合子小鼠相比，gp130基因敲除小鼠下颌骨矿化小梁骨的体积也减少，同时破骨细胞数量增加。这些结果表明，至少在胎儿发育期间，破骨细胞的形成并非完全依赖于gp130信号通路。gp130基因敲除小鼠中的破骨细胞性骨吸收可能是由IL-6家族以外的骨吸收激素和细胞因子的功能冗余引起的。
