Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada.
Exp Gerontol. 2009 Sep;44(9):613-8. doi: 10.1016/j.exger.2009.05.009. Epub 2009 Jun 6.
Increasing marrow adipogenesis plays a causative role in the pathogenesis of age-related bone loss that could be associated with high cytokine production. In this study, we characterized the age-related changes in cytokine expression by bone marrow (BM) adipocytes as compared with subcutaneous (SC) fat. BM and SC adipocytes were isolated from young (4 months) and old (24 months) male C57BL/6J. Total proteins were extracted and proteomic analysis of 96 cytokines was performed using a cytokine antibody array. Proteins showing a significant change were grouped according with their known function in bone. We found a significant age-induced difference in the expression of 53 cytokines. As compared with SC adipocytes, aging BM adipocytes showed a more pro-adipogenic, anti-osteoblastogenic and pro-apoptotic phenotype. These data suggest that, with aging, BM adipocytes become significantly more toxic than SC adipocytes. These cytokines, if secreted, could play a role in the pathogenesis of age-related bone loss by affecting other cells within the marrow milieu.
骨髓脂肪生成增加在与高细胞因子产生相关的与年龄相关的骨丢失发病机制中起因果作用。在这项研究中，我们比较了骨髓 (BM) 脂肪细胞与皮下 (SC) 脂肪的细胞因子表达的年龄相关性变化。从年轻（4 个月）和年老（24 个月）的雄性 C57BL/6J 中分离 BM 和 SC 脂肪细胞。提取总蛋白，并使用细胞因子抗体阵列对 96 种细胞因子进行蛋白质组学分析。根据它们在骨骼中的已知功能，将显示出显著变化的蛋白质进行分组。我们发现 53 种细胞因子的表达存在显著的年龄诱导差异。与 SC 脂肪细胞相比，衰老的 BM 脂肪细胞表现出更促脂肪生成、抗成骨细胞生成和促凋亡的表型。这些数据表明，随着年龄的增长，BM 脂肪细胞比 SC 脂肪细胞变得毒性更大。如果这些细胞因子被分泌，它们可能通过影响骨髓环境中的其他细胞在与年龄相关的骨丢失发病机制中发挥作用。
