Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis.
Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis.
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DOI：
10.1186/ar2719
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发表时间：
2009
影响因子：
4.9
通讯作者：
Lotz MK
中科院分区：
文献类型：
--
作者：
Grogan SP;Miyaki S;Asahara H;D'Lima DD;Lotz MK
最近的研究结果表明，关节软骨含有间充质祖细胞。本研究的目的是检查干细胞标志物（Notch-1、Stro-1和VCAM-1）和调节祖细胞分化的分子（Notch-1和Sox 9）在正常成人关节软骨和骨关节炎（OA）中的分布软骨。通过免疫组织化学（IHC）和流式细胞术分析标志物的表达。Hoechst 33342染料用于鉴定和分选软骨侧群（SP）。对SP和非SP（NSP）细胞进行多谱系分化测定，包括软骨形成、骨形成和脂肪形成。在整个正常软骨中，令人惊讶地高数量（>45%）的细胞对Notch-1、Stro-1和VCAM-1呈阳性。这些标记物在正常软骨的浅区（SZ）中的表达高于中间区（MZ）和深区（DZ）。非原纤化OA软骨SZ显示Notch-1和Sox 9染色频率降低，而MZ中Notch-1、Stro-1和VCAM-1阳性细胞增加。OA簇中的大多数细胞对测试的每个分子呈阳性。SP细胞在正常软骨和OA软骨中的分布频率为0.14 ± 0.05%，两者无显著性差异。SP细胞具有成软骨和成骨分化潜能，但不具有成脂分化潜能。这些结果显示在人软骨中表达推定的祖细胞标志物的细胞数量惊人地高。相比之下，SP细胞的百分比要低得多，并且在预期的干细胞频率范围内。因此，标记物如Notch-1、Stro-1或VCAM-1可能对鉴定软骨中的祖细胞没有用。相反，它们在OA软骨中的表达增加涉及OA特征性的异常细胞活化和分化过程。
Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage. Expression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells. A surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 ± 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential. These results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA.
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影响因子：
0.9
作者：
Gimeno, MJ;Maneiro, E;Blanco, FJ
通讯作者：
Blanco, FJ
影响因子：
--
作者：
Barbero, A;Ploegert, S;Martin, I
通讯作者：
Martin, I
影响因子：
4
作者：
Baddoo, M;Hill, K;Phinney, DG
通讯作者：
Phinney, DG
影响因子：
--
作者：
Fukui, Naoshi;Ikeda, Yasuko;Ochi, Takahiro
通讯作者：
Ochi, Takahiro
影响因子：
64.5
作者：
BENYA, PD;SHAFFER, JD
通讯作者：
SHAFFER, JD