Cytokine-like 1 (CYTL1) regulates the chondrogenesis of mesenchymal cells
Cytokine-like 1 (CYTL1) regulates the chondrogenesis of mesenchymal cells
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DOI：
10.1074/jbc.m700965200
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发表时间：
2007-10-05
影响因子：
4.8
通讯作者：
Chun, Jang-Soo
中科院分区：
文献类型：
--
作者：
Kim, Jae-Sung;Ryoo, Zae Young;Chun, Jang-Soo
为了寻找调控软骨发生和软骨发育的新分子，我们筛选了软骨特异表达序列标签数据库。细胞因子样1(Cytl1)是一种功能未知的候选细胞因子，最初在骨髓来源的CD34阳性细胞中被发现，用于功能鉴定。鉴于初步观察到Cytl1主要在软骨细胞和软骨中表达，我们探讨了其在软骨细胞形成和肥大性成熟中的可能作用。在体内和体外，间充质细胞中Cytl1的表达很低，在软骨形成过程中表达显著增加，在肥大成熟过程中表达降低。通过外源性Cytl1或异位表达Cytl1处理软骨间充质细胞，研究Cytl1在软骨形成和肥大成熟中的作用。值得注意的是，在微团培养过程中，外源Cytl1引起了小鼠肢芽间充质细胞的软骨分化。慢病毒介导的Cytl1过表达还能诱导间充质细胞向软骨方向分化。但Cytl1不影响软骨细胞的肥大成熟。Cytl1通过刺激Sox9转录活性发挥其软骨形成作用。此外，Cytl1可诱导胰岛素样生长因子1的表达，而胰岛素样生长因子1具有诱导软骨形成的能力。因此，我们的结果表明，软骨细胞特异性Cytl1作为一种新的自分泌因子调节软骨形成，但不能调控软骨细胞在软骨发育过程中的肥大成熟。
To identify novel molecules regulating chondrogenesis and cartilage development, we screened a cartilage-specific expressed sequence tag data base. Cytokine-like 1 (Cytl1), a possible cytokine candidate with unknown function that was originally identified in bone marrow-derived CD34-positive cells, was selected for functional characterization. In view of the initial observation that Cytl1 is predominantly expressed in chondrocytes and cartilage, we investigated its possible role in chondrogenesis and hypertrophic maturation of chondrocytes. Cytl1 expression was very low in mesenchymal cells, dramatically increased during chondrogenesis, and decreased during hypertrophic maturation, both in vivo and in vitro. The role of Cytl1 in chondrogenesis and hypertrophic maturation was examined by treating chondrifying mesenchymal cells with exogenous Cytl1 or ectopic expression of Cytl1. Notably, exogenous Cytl1 caused chondrogenic differentiation of mouse limb bud mesenchymal cells during micromass culture. Lentivirus-mediated overexpression of Cytl1 additionally induced chondrogenic differentiation of mesenchymal cells. However, Cytl1 did not affect the hypertrophic maturation of chondrocytes. Cytl1 exerted its chondrogenic effect via stimulation of Sox9 transcriptional activity. In addition, Cytl1 caused expression of insulin-like growth factor 1, which has a capacity to induce chondrogenesis. Thus, our results collectively suggest that chondrocyte-specific Cytl1 regulates chondrogenesis as a novel autocrine factor, but not hypertrophic maturation of chondrocytes during cartilage development.