Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow.

Mesenchymal progenitors residing close to the bone surface are functionally distinct from those in the central bone marrow.
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DOI:
10.1016/j.bone.2012.12.013
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发表时间:
2013-04
期刊:
影响因子:
4.1
通讯作者:
Qin, Ling
Qin, Ling
中科院分区:
医学2区
文献类型:
--
作者:
Siclari, Valerie A.;Zhu, Ji;Akiyama, Kentaro;Liu, Fei;Zhang, Xianrong;Chandra, Abhishek;Nah, Hyun-Duck;Shi, Songtao;Qin, Ling

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长骨是一种解剖结构复杂的组织,两端是富含小梁的干骺端,中部是富含皮质的骨干。传统的冲洗方法只能从长骨的中心区域分离间充质祖细胞,这些细胞远离骨表面。我们提出,间充质祖细胞居住在骨内膜骨髓,是接近骨形成的网站,如骨小梁和骨内膜,表现出不同的中央骨髓。在这份报告中,我们单独分离骨内膜骨髓使用一种独特的酶消化方法,并证明它包含一个更高的频率比中央骨髓间充质祖细胞。骨内膜间充质祖细胞表达传统的间充质干细胞标志物,并能够多谱系分化。然而,我们发现从骨髓不同解剖区域分离的间充质祖细胞确实表现出重要的功能差异。与其中央骨髓对应物相比,骨内膜间充质祖细胞具有上级增殖能力,细胞周期抑制剂的表达减少。它们在培养物和炎症性肠病小鼠模型中显示出更大的免疫抑制活性。老化是导致骨小梁丢失的主要因素。我们发现,老年小鼠与年轻小鼠相比,骨内膜间充质祖细胞的数量显著减少。甲状旁腺激素(PTH)治疗有效地刺激骨形成。一个单一的PTH注射大大增加了骨内膜间充质祖细胞的数量,特别是那些位于干骺端骨,但没有影响他们的中央同行。总之,骨内膜间充质祖细胞比中央间充质祖细胞代谢更活跃,与生理性骨形成相关。因此,它们代表了未来间充质干细胞研究的生物学重要靶点。
Long bone is an anatomically complicated tissue with trabecular-rich metaphyses at two ends and cortical-rich diaphysis at the center. The traditional flushing method only isolates mesenchymal progenitor cells from the central region of long bones and these cells are distant from the bone surface. We propose that mesenchymal progenitors residing in endosteal bone marrow that is close to the sites of bone formation, such as trabecular bone and endosteum, behave differently from those in the central bone marrow. In this report, we separately isolated endosteal bone marrow using a unique enzymatic digestion approach and demonstrated that it contained a much higher frequency of mesenchymal progenitors than the central bone marrow. Endosteal mesenchymal progenitors express traditional mesenchymal stem cell markers and are capable of multi-lineage differentiation. However, we found that mesenchymal progenitors isolated from different anatomical regions of the marrow did exhibit important functional differences. Compared to their central marrow counterparts, endosteal mesenchymal progenitors have superior proliferative ability with reduced expression of cell cycle inhibitors. They showed greater immunosuppressive activity in culture and in a mouse model of inflammatory bowel disease. Aging is a major contributing factor for trabecular bone loss. We found that old mice have a dramatically decreased number of endosteal mesenchymal progenitors compared to young mice. Parathyroid hormone (PTH) treatment potently stimulates bone formation. A single PTH injection greatly increased the number of endosteal mesenchymal progenitors, particularly those located at the metaphyseal bone, but had no effect on their central counterparts. In summary, endosteal mesenchymal progenitors are more metabolically active and relevant to physiological bone formation than central mesenchymal progenitors. Hence, they represent a biologically important target for future mesenchymal stem cell studies.
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发表时间: 2009-02
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发表时间: 2012-09-01
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DOI: 10.1111/j.1365-2184.1970.tb00347.x
发表时间: 1970-01-01
期刊: CELL AND TISSUE KINETICS
影响因子: --
作者:
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