Estrogen-induced osteogenesis in mice is associated with the appearance of Cbfa1-expressing bone marrow cells
Estrogen-induced osteogenesis in mice is associated with the appearance of Cbfa1-expressing bone marrow cells
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DOI：
10.1002/jcb.10021
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Tobias, JH
中科院分区：
文献类型：
--
作者：
Plant, A;Samuels, A;Tobias, JH
cbfa 1是一种转录因子，被认为在胚胎骨骼发生过程中参与早期成骨细胞分化。为了确定Cbfa 1是否在成人骨形成中发挥类似的作用，我们分析了其表达是否在雌激素诱导的成骨过程中发生变化，我们最近的研究表明，这种反应涉及骨髓内早期成骨细胞前体的产生。为了便于鉴定表达Cbfa 1的细胞，使用β-半乳糖苷酶（lacZ）作为遗传标记，在cbfa 1基因缺失（cbfa 1（-/-））杂合小鼠中进行这些研究。通过lacZ染色胫骨近端干骺端纵切片鉴定Cbfa 1表达细胞。用17 β-雌二醇0. 5 mg/周治疗cbfa 1小鼠24天导致新的松质骨表面出现。这种反应与干骺端内表达Cbfa 1的细胞数量显著增加相关，不仅包括骨表面上的成骨细胞，还包括邻近骨髓内的细胞。随后，我们列举了Cbfa 1表达细胞在较早的时间点后，雌激素，在切片共染色的ALP活性。雌激素处理4天后，骨髓腔内出现一群表达Cbfa 1但ALP阴性的细胞。在随后的时间点，仍存在大量的Cbfa 1+骨髓细胞，但其中大多数靠近显示高水平ALP活性的部位的新骨小梁表面。在进一步的研究中，通过免疫组织化学分析野生型小鼠中的Cbfa 1表达，观察到Cbfa 1表达细胞的等效分布。我们的结论是，雌激素诱导的成骨与骨髓中的Cbfa 1表达细胞群的出现有关，我们假设这代表了负责随后新骨形成的成骨细胞前体群。(C)2001 Wiley-Liss，Inc.
Cbfa1 is a transcription factor recognised as being involved in early osteoblast differentiation during embryonic skeletogenesis. To determine whether Cbfa1 plays a similar role in bone formation in the adult, we analysed whether its expression is altered during estrogen-induced osteogenesis, following our recent studies which suggest that this response involves the generation of early osteoblast precursors within bone marrow. To facilitate identification of Cbfa1-expressing cells, these studies were performed in mice heterozygous for a cbfa1 gene deletion (cbfa1(-/-)) using beta -galactosidase (lacZ) as a genetic marker. Cbfa1-expressing cells were identified by lacZ staining of longitudinal sections of the proximal tibial metaphysis. Treatment of cbfa1 mice with 17 beta -estradiol 0.5 mg/week for 24 days led to the appearance of new cancellous bone surfaces. This response was associated with a marked increase in number of Cbfa1 expressing cells within the metaphysis, consisting not only of osteoblasts on bone surfaces but also of cells within the adjacent bone marrow. We subsequently enumerated Cbfa1-expressing cells at earlier time-points following estrogen, in sections co-stained for ALP activity. After 4 days of estrogen treatment, a population of cells appeared within the marrow cavity which expressed Cbfa1, but were negative for ALP. At later time-points, large numbers of Cbfa1 + bone marrow cells were still present, but the majority of these were close to new trabecular bone surfaces at sites which showed high levels of ALP activity. An equivalent distribution of Cbfa1-expressing cells was observed in further studies where Cbfa1 expression was analysed in wild-type mice by immunohistochemistry. We conclude that estrogen-induced osteogenesis is associated with the appearance of a population of Cbfa1-expressing cells within bone marrow, which we hypothesize to represent the osteoblast precursor population responsible for subsequent new bone formation. (C) 2001 Wiley-Liss, Inc.