Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence
Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence
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DOI：
10.1172/jci118600
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发表时间：
1996-04-01
影响因子：
15.9
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Jilka, RL;Weinstein, RS;Manolagas, SC
骨髓是破骨细胞生成和成骨细胞生成的主要场所;前者的增加与性腺类固醇的急性损失引起的骨丢失有关。我们现在已经使用了一种建立的加速衰老和骨质减少的小鼠模型（SAMP 6）来检验成骨细胞生成减少与骨量减少有关的假设。在1月龄时，SAMP 6骨髓中的成骨祖细胞数量与对照组无差别;然而，在3-4月龄时发现减少了3倍。成骨细胞形成受损与骨形成减少和骨矿物质密度降低在时间上相关，如分别通过四环素标记的松质骨的组织形态计量学分析和双能X线吸收测定法所确定的，在这些小鼠中，在离体骨髓培养物中测定的破骨细胞生成也减少，组织切片中的破骨细胞数量也减少。此外，与对照组不同，加速衰老小鼠在性腺切除术后未能增加破骨细胞的发育，破骨细胞生成缺陷是继发于成骨细胞形成受损，这一事实证明，破骨细胞生成可以通过添加正常小鼠的成骨细胞来恢复。这些发现首次证明了低骨矿物质密度和骨髓中成骨细胞生成减少之间的联系，并验证了衰老加速小鼠作为退化性骨质减少模型的有效性。
Bone marrow is the principal site for osteoclastogenesis and osteoblastogenesis; and an increase in the former has been linked with bone loss caused by acute loss of gonadal steroids, We have now used an established murine model of accelerated senescence and osteopenia (SAMP6) to test the hypothesis that reduced osteoblastogenesis is linked with decreased bone mass. At 1 mo of age, the number of osteoblast progenitors in SAMP6 marrow was indistinguishable from controls; however a threefold decrease was found at 3-4 mo of age, Impaired osteoblast formation was temporally associated with decreased bone formation and decreased bone mineral density, as determined by histomorphometric analysis of tetracycline-labeled cancellous bone and dual-energy x-ray absorptiometry, respectively, Osteoclastogenesis determined in ex vivo bone marrow cultures was also decreased in these mice, as was the number of osteoclasts in histologic sections, Moreover, unlike controls, senescence-accelerated mice failed to increase osteoclast development after gonadectomy, The osteoclastogenesis defect was secondary to impaired osteoblast formation as evidenced by the fact that osteoclastogenesis could be restored by addition of osteoblastic cells from normal mice. These findings provide the first demonstration of a link between low bone mineral density and decreased osteoblastogenesis in the bone marrow and validate the senescence-accelerated mouse as a model of involutional osteopenia.