The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGF(beta) and 1,25(OH(2)) vitamin D(3).
The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGF(beta) and 1,25(OH(2)) vitamin D(3).
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DOI：
10.1016/s0024-3205(02)01548-5
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发表时间：
2002-05
期刊：
影响因子：
6.1
通讯作者：
Matthew J Shiels;A. Mastro;C. Gay
中科院分区：
文献类型：
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作者：
Matthew J Shiels;A. Mastro;C. Gay
衰老骨中成骨细胞功能的丧失是骨质减少或骨量丢失的主要原因之一。在这项研究中，通过检测大鼠长骨骨膜成骨细胞对TGFβ 1和1，25-二羟基维生素D3（1，25-D3）的增殖反应作为供体年龄的函数来研究这种功能丧失。使用DNA结合荧光染料，在用两种浓度（10− 9 M或10− 12 M）的1，25-D3或TGFβ 1或溶剂处理后，测量来自年轻成年（3-4个月）或老年（14-15个月）大鼠的成骨细胞培养物中的DNA水平。当用1，25-D3处理时，来自年轻大鼠骨的细胞显示出当用较高剂量处理时增殖的剂量依赖性增加和当用较低剂量处理时增殖的减少。从老年大鼠分离的成骨细胞对1，25-D3处理无反应。发现对TGFβ 1的反应模式相似，当用10− 9 M TGFβ1处理时，年轻大鼠成骨细胞的增殖率增加，但老年大鼠来源的细胞无反应。10 - 12 M剂量的TGFβ 1对年轻和年老的细胞都无效。这项研究表明，来自老年供体的成骨细胞对维生素D和TGFβ（骨骼发育和维持的两个主要控制因素）的反应能力受损。
The loss of osteoblast function in aging bone is one of the major causes of osteopenia, or loss of bone mass. In this study, this loss of function was investigated by examining the proliferative response of rat long bone periosteal osteoblasts to TGFβ1and 1,25-dihydroxy vitamin D3(1,25-D3) as a function of donor age. Using a DNA binding fluorescent dye, DNA levels were measured in osteoblast cultures derived from either young adult (3–4 months) or old (14–15 months) rats following treatment with two concentrations (10−9M or 10−12M) of either 1,25-D3or TGFβ1or with vehicle. Cells from young rat bone, when treated with 1, 25-D3, showed a dose-dependent increase in proliferation when treated with the higher dose and a decrease in proliferation when treated with the lower dose. Osteoblasts isolated from old rats did not respond to 1, 25-D3treatment. A similar pattern of response to TGFβ1was found. When treated with 10−9M TGFβ1, the rate of proliferation increased for young rat osteoblasts, but the old rat derived cells were unresponsive. The 10−12M dose of TGFβ1was ineffective for both young and old cells. This study has shown that osteoblasts derived from old donors are impaired in their ability to respond to vitamin D and TGFβ, two of the major controlling factors of skeletal development and maintenance.