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Estrogen‐induced osteogenesis in mice is associated with the appearance of Cbfa1‐expressing bone marrow cells
Author(s) -
Plant Andrea,
Samuels Abigail,
Perry Mark J.,
Colley Shane,
Gibson Rachel,
Tobias Jonathan H.
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10021
Subject(s) - bone marrow , osteoblast , bone cell , metaphysis , estrogen , cancellous bone , population , pathology , medicine , endocrinology , biology , anatomy , in vitro , genetics , environmental health
Abstract 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 β‐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 17β‐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. J. Cell. Biochem. 84: 285–294, 2002. © 2001 Wiley‐Liss, Inc.