Torreggiani Elena, Matthews Brya G, Pejda Slavica, Matic Igor, Horowitz Mark C, Grcevic Danka, Kalajzic Ivo
Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
PLoS One. 2013 Sep 6;8(9):e75204. doi: 10.1371/journal.pone.0075204. eCollection 2013.
Presently there is no clear evidence for the ability of mature osteogenic lineage cells to dedifferentiate. In order to identify and trace mature osteogenic lineage cells, we have utilized transgenic mouse models in which the dentin matrix protein 1 (Dmp1) promoter drives expression of GFP (active marker) or Cre recombinase (historic label) in preosteocytes/osteocytes. In long bone chip outgrowth cultures, in which cells on the bone surface were enzymatically removed, cells with previous activity of the Dmp1 promoter migrated onto plastic and down-regulated Dmp1-GFP expression. Dmp1Cre-labeled cells from these cultures had the potential to re-differentiate into the osteogenic lineage, while the negative population showed evidence of adipogenesis. We observed numerous Dmp1Cre-labeled osteoblasts on the surface of bone chips following their in vivo transplantation. Our data indicate that cells embedded in bone matrix are motile, and once given access to the extra bony milieu will migrate out of their lacunae. This population of cells is phenotypically and functionally heterogeneous in vitro. Once the preosteocytes/osteocytes leave lacunae, they can dedifferentiate, potentially providing an additional source of functional osteoblasts.
目前，尚无明确证据表明成熟的成骨谱系细胞具有去分化能力。为了识别和追踪成熟的成骨谱系细胞，我们利用了转基因小鼠模型，其中牙本质基质蛋白1（Dmp1）启动子驱动绿色荧光蛋白（活性标记）或Cre重组酶（历史标记）在前成骨细胞/成骨细胞中表达。在长骨芯片生长培养中，通过酶法去除骨表面的细胞，具有Dmp1启动子先前活性的细胞迁移到塑料上并下调Dmp1-绿色荧光蛋白的表达。来自这些培养物的Dmp1Cre标记细胞具有重新分化为成骨谱系的潜力，而阴性群体则显示出脂肪生成的证据。在体内移植后，我们在骨芯片表面观察到大量Dmp1Cre标记的成骨细胞。我们的数据表明，嵌入骨基质中的细胞具有运动性，一旦进入骨外环境，它们就会从其腔隙中迁移出来。这群细胞在体外具有表型和功能的异质性。一旦前成骨细胞/成骨细胞离开腔隙，它们就可以去分化，这可能为功能性成骨细胞提供额外的来源。
