Aged mice require full transcription factor, Runx2/Cbfa1, gene dosage for cancellous bone regeneration after bone marrow ablation
Aged mice require full transcription factor, Runx2/Cbfa1, gene dosage for cancellous bone regeneration after bone marrow ablation
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DOI：
10.1359/jbmr.040601
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发表时间：
2004-09-01
影响因子：
6.2
通讯作者：
Noda, M
中科院分区：
文献类型：
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作者：
Tsuji, K;Komori, T;Noda, M
Runx2是体内成骨细胞分化的先决条件。为了阐明Runx2基因在成年骨代谢中的功能，我们对Runx2杂合基因敲除小鼠进行了骨髓切除，发现老年(但不是年轻)成年Runx2杂合基因敲除小鼠骨髓去除后新骨形成能力降低。我们还发现，老年Runx2杂合基因敲除小鼠的骨髓细胞在体外降低了ALP(+)集落形成能力。这表明在成年小鼠中维持成骨细胞活性需要完整的Runx2剂量。简介：Runx2基因的零突变导致成骨细胞分化的完全丧失，杂合性Runx2缺乏会导致人和小鼠的锁骨颅骨发育不良。然而，Runx2基因在成人骨代谢中的作用尚不清楚。因此，我们研究了Runx2基因杂合性缺失的成年小鼠对Runx2基因功能的影响。材料和方法：对青年(2.5+/-0.5月龄)和老年(7.5+/-0.5月龄)Runx2杂合基因敲除小鼠和野生型(WT)小鼠进行骨髓消融。结果：虽然WT小鼠骨髓去除后在手术后的骨髓腔中观察到了新的骨形成，但在Runx2杂合基因敲除小鼠中，这种骨形成明显减少。有趣的是，这种效应只在老年小鼠身上观察到，但在年轻成年小鼠身上观察不到。老年小鼠Runx2杂合子缺陷使骨髓细胞培养中碱性磷酸酶(ALP)(+)细胞集落数量显著减少，表明骨祖细胞数量减少。杂合子Runx2基因缺陷对体外培养的成骨细胞的影响仅限于老年小鼠的细胞，而在幼年小鼠的骨髓细胞培养中未观察到这种作用。结论：成年小鼠骨髓去除后松质骨形成需要Runx2的全基因剂量。
Runx2 is prerequisite for the osteoblastic differentiation in vivo. To elucidate Runx2 gene functions in adult bone metabolism, we conducted bone marrow ablation in Runx2 heterozygous knockout mice and found that aged (but not young) adult Runx2 heterozygous knockout mice have reduced new bone formation capacity after bone marrow ablation. We also found that bone marrow cells from aged Runx2 heterozygous knockout mice have reduced ALP(+) colony-forming potential in vitro. This indicates that full Runx2 dosage is needed for the maintenance of osteoblastic activity in adult mice.Introduction: Null mutation of the Runx2 gene results in total loss of osteoblast differentiation, and heterozygous Runx2 deficiency causes cleidocranial dysplasia in humans and mice. However, Runx2 gene functions in adult bone metabolism are not known. We therefore examined the effects of Runx2 gene function in adult mice with heterozygous loss of the Runx2 gene. Materials andMethods: Bone marrow ablation was conducted in young adult (2.5 +/- 0.5 months old) or aged adult (7.5 +/- 0.5 months old) Runx2 heterozygous knockout mice and wildtype (WT) littermates. Cancellous bone regeneration was evaluated by 2D muCT.Results: Although new bone formation was observed after bone marrow ablation in the operated bone marrow cavity of WT mice, such bone formation was significantly reduced in Runx2 heterozygous knockout mice. Interestingly, this effect was observed specifically in aged but not young adult mice. Runx2 heterozygous deficiency in aged mice significantly reduced the number of alkaline phosphatase (ALP)(+) cell colonies in the bone marrow cell cultures, indicating a reduction in the numbers of osteoprogenitor cells. Such effects of heterozygous Runx2 deficiency on osteoblasts in vitro was specific to the cells from aged adult mice, and it was not observed in the cultures of marrow cells from young adult mice.Conclusion: These results indicate that full gene dosage of Runx2 is required for cancellous bone formation after bone marrow ablation in adult mice.