Parathyroid hormone activates adhesion in bone marrow stromal precursor cells
Parathyroid hormone activates adhesion in bone marrow stromal precursor cells
复制标题
DOI：
10.1677/joe.0.1800505
复制
发表时间：
2004-03-01
影响因子：
4
通讯作者：
Chambers, TJ
中科院分区：
文献类型：
--
作者：
Davies, J;Chambers, TJ
甲状旁腺激素（PTH）促进骨形成的能力最近已被用于治疗骨质疏松症。然而，其潜在机制尚不清楚。成骨细胞是骨形成细胞，在体外培养时来源于称为成纤维细胞集落形成单位（CFU-F）的多潜能骨髓基质前体细胞，这种基质前体细胞与骨的粘附可能是骨对PTH的合成代谢反应的早期事件。为了验证这一点，我们测量了在施用合成代谢剂量的PTH后可以从小鼠骨髓中提取的CFU-F的数量。我们发现，非常早期的反应是从2小时内开始，从骨髓中提取的CFU-F数量急剧减少。然后，我们测试了PTH是否具有体外激活CFU-F粘附的能力。为此，将骨髓细胞在PTH中孵育不同的时间。然后除去非粘附细胞，并将粘附细胞在无PTH培养基中孵育14天，以作为集落形成来评估在前一时期粘附的CFU-F的数量。我们发现，在PTH中孵育导致在24小时内粘附的CFU-F的数量大幅增加。这种增加被整联蛋白的肽抑制剂消除。这种增加似乎不是通过PTH诱导的白细胞介素-6增加介导的，因为白细胞介素-6取代PTH时对CFU-F数量没有影响。同样，粘附不受骨髓细胞在二丁酰环AMP中孵育的影响，也不受一氧化氮抑制剂或供体的影响。然而，PTH在体外激活CFU-F被吲哚美辛强烈抑制，并被前列腺素E-2模拟，吲哚美辛逆转PTH介导的CFU-F减少，可以从小鼠骨髓中提取。这些结果表明，PTH快速激活CFU-F粘附到塑料或骨表面。这种激活可能代表骨细胞对PTH的合成代谢反应的早期事件。
The ability of parathyroid hormone (PTH) to enhance bone formation has recently been exploited in the treatment of osteoporosis. However, the underlying mechanisms are unknown. Osteoblasts, the bone-forming cells, derive from multipotential bone marrow stromal precursors called colony-forming units-fibroblastic (CFU-F) upon culture ex vivo, Adhesion of such stromal precursors to bone is likely to be an early event in the anabolic response of bone to PTH. To test this, We Measured the number of CFU-F that could be extracted from murine bone marrow after administration of in anabolic dose of PTH. We found that a very early response is a dramatic reduction, starting within 2 h, in the number of CFU-F that could be extracted from their bone marrow. We then tested whether PTH has the ability to activate adhesion of CFU-F in vitro. For this, bone marrow cells were incubated in PTH for varying times. Non-adherent cells were then removed, and the adherent cells were incubated in PTH-free medium for 14 days to assess, as colony formation, the number of CFU-F that had adhered in the preceding period. We found that incubation in PTH caused a substantial increase in the number of CFU-F that adhered within 24 h. This increase was abrogated by peptidic inhibitors of integrins. The increase did not seem to be mediated through a PTH-induced increase in interleukin-6, since interleukin-6 had no effect on CFU-F numbers when substituted for PTH. Similarly, adhesion was unaffected by incubation of bone marrow cells in dibutyryl cyclic AMP, nor by inhibitors or donors of nitric oxide. However, activation of CFU-F in vitro by PTH was strongly inhibited by indomethacin and mimicked by prostaglandin E-2, and indomethacin reversed the PTH-mediated reduction of CFU-F that could be extracted from mouse bone marrow. These results suggested that PTH rapidly activates adhesion of CFU-F to plastic or bone surfaces. This activation may represent an early event in the anabolic response of bone cells to PTH.