Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia
Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia
复制标题
DOI：
10.1359/jbmr.1997.12.11.1772
复制
发表时间：
1997-11-01
影响因子：
6.2
通讯作者：
Lipschitz, DA
中科院分区：
文献类型：
--
作者：
Kajkenova, O;LeckaCzernik, B;Lipschitz, DA
骨形成和造血在解剖学上是并列的，并且具有共同的调节机制，然而，对这两个过程之间的相互关系知之甚少。我们之前已经证明，衰老加速小鼠-P6（SAMP 6）表现出骨髓中成骨细胞生成减少，这在时间上与骨形成率低和骨矿物质密度降低有关。在这里，我们报告说，与成骨细胞生成减少相反，与SAMR 1相比，来自SAMP 6小鼠的离体骨髓培养物显示出集落形成单位脂肪细胞数量的增加，以及完全分化的骨髓脂肪细胞数量的增加。此外，来自SAMP 6的长期骨髓培养物更快地产生粘附的基质层，产生了显著更多的骨髓祖细胞，并产生了更多的IL-6和集落刺激活性。与此一致，来自SAMP 6小鼠的新鲜分离的骨髓中的骨髓细胞的数量增加，外周血中的粒细胞的数量也增加。SAMP 6小鼠表现出成骨细胞生成减少的证据，以及增加的脂肪生成和骨髓生成，强烈地表明多潜能间充质祖细胞的分化程序的转换可能是这些动物的骨骼和其它组织中表现出的异常表型的基础。此外，这些观察结果支持了成骨细胞生成和脂肪生成之间存在相互关系的论点，在动物和人类中，随着年龄的增长，骨形成减少和由此导致的骨质减少与骨髓肥胖增加的相关性。
Bone formation and hematopoiesis are anatomically juxtaposed and share common regulatory mechanisms, However, little is known about the interrelationship between these two processes. We have previously shown that the senescence accelerated mouse-P6 (SAMP6) exhibits decreased osteoblastogenesis in the bone marrow that is temporally linked with a low rate of bone formation and decreased bone mineral density. Here we report that in contrast to decreased osteoblastogenesis, ex vivo bone marrow cultures from SAMP6 mice exhibited an increase in the number of colony-forming unit adipocytes, as well as an increase in the number of fully differentiated marrow adipocytes, compared with SAMR1 (nonosteopenic) controls, Further, long-term bone marrow cultures from SAMP6 produced an adherent stromal layer more rapidly, generated significantly more myeloid progenitors and produced more IL-6 and colony-stimulating activity, Consistent with this, the number of myeloid cells in freshly isolated marrow from SAMP6 mice was increased, as was the number of granulocytes in peripheral blood, The evidence that SAMP6 mice exhibit decreased osteoblastogenesis, and increased adipogenesis and myelopoiesis, strongly suggests that a switch in the differentiation program of multipotential mesenchymal progenitors may underlie the abnormal phenotype manifested in the skeleton and other tissues of these animals, Moreover, these observations support the contention for the existence of a reciprocal relationship between osteoblastogenesis and adipogenesis that may explain the association of decreased bone formation and the resulting osteopenia with the increased adiposity of the marrow seen with advancing age in animals and humans.