The Expression of IL-6 by Osteoblasts Is Increased in Healthy Elderly Individuals: Stimulated Proliferation and Differentiation Are Unaffected by Age
The Expression of IL-6 by Osteoblasts Is Increased in Healthy Elderly Individuals: Stimulated Proliferation and Differentiation Are Unaffected by Age
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DOI：
10.1007/s00223-010-9412-x
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发表时间：
2010-11-01
影响因子：
4.2
通讯作者：
Langdahl, Bente Lomholt
中科院分区：
文献类型：
--
作者：
Eriksen, Charlotte Grith;Olsen, Helene;Langdahl, Bente Lomholt
随着年龄的增长，骨矿物质含量减少，骨折风险增加。这是由于与破骨细胞相比，成骨细胞相对不足造成的。因此，我们想要研究从年轻人和老年人中获得的人成骨细胞（hOB）在增殖、分化和细胞因子表达方面的潜在差异。从11名老年人（73-85岁）和15名年轻人（21-27岁）健康个体获得hOB培养物。用hGH、IGF-I、hGH + IGF-I和TGF-β 1刺激细胞。通过胸苷掺入评价增殖，通过碱性磷酸酶、OPG和PINP产生评价分化。使用实时PCR和三种精心选择的管家基因研究IL-6、TGF-β 1、OPG和RANKL的表达。hGH和IGF-I的联合刺激增加了增殖，而从年轻人和老年人中获得的hOB之间没有差异。来自年轻个体的hOB对维生素D刺激有反应，碱性磷酸酶更明显增加：107 +/- A 17% vs. 43 +/- A 5%，P < 0.01。TGF-β 1刺激可降低老年人hOB的OPG生成，但对年轻人无影响，P < 0.05。与年轻人hOB相比，老年人hOB表达IL-6 mRNA（P < 0.05），而OPG和TGF-β 1 mRNA（分别为P = 0.08和P = 0.08）较低。总之，来自老年个体的hOB比来自年轻个体的hOB表达更多的IL-6 mRNA和更少的OPG和TGF-β 1 mRNA。这可以部分解释老年人骨量减少和骨折风险增加的原因。来自年轻人和老年人的hOB对增殖和分化的短期刺激的反应相似。
Increasing age is associated with reduced bone mineral content and increased risk of fractures. This is caused by a relative insufficiency of osteoblasts compared with osteoclasts. We therefore wanted to examine the potential differences in proliferation, differentiation, and expression of cytokines between human osteoblasts (hOBs) obtained from young and elderly individuals. Cultures of hOBs were obtained from 11 elderly (73-85 years) and 15 young (21-27 years) healthy individuals. The cells were stimulated with hGH, IGF-I, hGH + IGF-I, and TGF-beta 1. Proliferation was evaluated by thymidine incorporation, and differentiation was evaluated by alkaline phosphatase, OPG, and PINP production. Expression of IL-6, TGF-beta 1, OPG, and RANKL was investigated using real-time PCR and three carefully selected housekeeping genes. Combined stimulation with hGH and IGF-I increased proliferation without differences between hOBs obtained from young and elderly individuals. hOBs from young individuals responded to stimulation with vitamin D with a more pronounced increase in alkaline phosphatase: 107 +/- A 17% vs. 43 +/- A 5%, P < 0.01. Stimulation with TGF-beta 1 decreased OPG production by hOBs from elderly individuals but not from young individuals, P < 0.05. hOBs from elderly individuals expressed significantly higher amounts of IL-6 mRNA (P < 0.05) and less OPG and TGF-beta 1 mRNA (P = 0.08 and P = 0.08, respectively) compared with hOBs from young individuals. In conclusion, hOBs from elderly individuals express more IL-6 mRNA and less OPG and TGF-beta 1 mRNA than hOBs from young individuals. This could partly explain the reduced bone mass and increased fracture risk seen in the elderly. hOBs from young and elderly individuals responded similarly to short-term stimulation of proliferation and differentiation.