Stimulation of chondrocyte hypertrophy by chemokine stromal cell-derived factor 1 in the chondro-osseous junction during endochondral bone formation.
Stimulation of chondrocyte hypertrophy by chemokine stromal cell-derived factor 1 in the chondro-osseous junction during endochondral bone formation.
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DOI：
10.1016/j.ydbio.2010.02.033
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Wei L;Kanbe K;Lee M;Wei X;Pei M;Sun X;Terek R;Chen Q
在软骨内骨形成过程中，软骨细胞在被骨和骨髓取代之前经历向肥大的分化。在这项研究中，我们发现，G-蛋白偶联受体CXCR 4主要表达在肥大的软骨细胞，而其配体，趋化因子基质细胞衍生因子1（SDF-1）的表达在骨髓中相邻的肥大软骨细胞。因此，它们在生长板的软骨-骨连接处以互补模式表达。将CXCR 4 cDNA转染到肥大前软骨细胞中导致肥大标志物包括Runx 2、Col X和MMP-13响应于SDF-1处理的剂量依赖性增加。在器官培养中，SDF-1浸润软骨并加速生长板肥大。此外，持续输注SDF-1到兔胫骨近端骺板导致早期骺板闭合，这伴随着X型胶原表达的短暂升高。阻断SDF-1/CXCR 4相互作用抑制Runx 2的表达。因此，SDF-1和CXCR 4的相互作用是Runx 2表达所必需的。有趣的是，敲低Runx 2基因表达导致肥大软骨细胞中CXCR 4 mRNA水平降低。这表明SDF-1/CXCR 4刺激软骨细胞肥大的正反馈回路，其由Runx 2介导。
During endochondral bone formation, chondrocytes undergo differentiation toward hypertrophy before they are replaced by bone and bone marrow. In this study, we found that a G-protein coupled receptor CXCR4 is predominantly expressed in hypertrophic chondrocytes, while its ligand, chemokine stromal cell derived factor 1 (SDF-1) is expressed in the bone marrow adjacent to hypertrophic chondrocytes. Thus, they are expressed in a complementary pattern in the chondro-osseous junction of the growth plate. Transfection of a CXCR4 cDNA into pre-hypertrophic chondrocytes results in a dose-dependent increase of hypertrophic markers including Runx2, Col X, and MMP-13 in response to SDF-1 treatment. In organ culture SDF-1 infiltrates cartilage and accelerates growth plate hypertrophy. Furthermore, a continuous infusion SDF-1 into the rabbit proximal tibial physis results in early physeal closure, which is accompanied by a transient elevation of type X collagen expression. Blocking SDF-1/CXCR4 interaction suppresses the expression of Runx2. Thus, interaction of SDF-1 and CXCR4 is required for Runx2 expression. Interestingly, knocking down Runx2 gene expression results in a decrease of CXCR4 mRNA levels in hypertrophic chondrocytes. This suggests a positive feedback loop of stimulation of chondrocyte hypertrophy by SDF-1/CXCR4, which is mediated by Runx2.
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影响因子：
7.8
作者：
GIBSON, GJ;FLINT, MH
通讯作者：
FLINT, MH
影响因子：
4.9
作者：
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通讯作者：
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DOI：
10.1073/pnas.95.16.9448
发表时间：
1998-08-04
影响因子：
11.1
作者：
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通讯作者：
Springer, TA
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影响因子：
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作者：
Uchimura, Kenji;Morimoto-Tomita, Megumi;Bistrup, Annette;Li, Jessica;Lyon, Malcolm;Gallagher, John;Werb, Zena;Rosen, Steven D
通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
Lapidot, T