The influence of Chm-I knockout on ectopic cartilage regeneration and homeostasis maintenance.
The influence of Chm-I knockout on ectopic cartilage regeneration and homeostasis maintenance.
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DOI：
10.1089/ten.tea.2014.0277
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发表时间：
2015-01
影响因子：
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通讯作者：
Yueqian Zhu;Yingying Zhang;Yu Liu;R. Tao;Huitang Xia;Rui Zheng;Yuan Shi;Shengjian Tang
中科院分区：
文献类型：
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作者：
Yueqian Zhu;Yingying Zhang;Yu Liu;R. Tao;Huitang Xia;Rui Zheng;Yuan Shi;Shengjian Tang
骨髓间充质干细胞（MSC）再生软骨的异位骨化严重限制了其修复鼻、耳廓等皮下软骨缺损的应用。与MSCs不同的是，软骨细胞在异位微环境中能保持稳定的成软骨表型，推测与抗血管生成因子Chm-I的存在有关。因此，本研究的目的是阐明Chm-I是否是软骨细胞稳定异位成软骨所必需的，这可能有助于解决MSC异位骨化的问题。目前的研究表明，Chm-I基因敲除对原位关节软骨发育没有明显影响。然而，来自Chm-I敲除（Chm-I（-/-），KO）而非野生型（WT）小鼠的天然关节软骨在皮下植入裸鼠16天后显示出明显的骨化。有趣的是，细胞形态，软骨特异性基质表达，和小球培养证明，Chm-I敲除软骨细胞在体外的表型，功能和软骨形成能力没有明显的影响，除了在WT组中的细胞增殖比KO组中的细胞快一点。然而，Chm-I基因敲除直接干扰体内异位软骨再生时，软骨细胞皮下注射到裸鼠与基质胶。此外，Chm-I基因敲除明显损害了皮下植入后体外再生软骨的异位稳定性。这些结果表明，Chm-I是异位软骨再生和维持软骨稳态不可或缺的因子，为解决MSC再生软骨在异位龛中的稳定性问题提供了线索。此外，本研究还提供了一种基于组织工程策略的新模型，以正确评估其他靶基因的功能。
Ectopic ossification of mesenchymal stem cell (MSC) regenerated cartilage has greatly restricted its application in repairing subcutaneous cartilage defects (such as nasal or auricular). Different from MSCs, chondrocytes can maintain stable chondrogenic phenotype in ectopic microenvironment, which was speculated to be related with the existence of antiangiogenic factors such as Chondromodulin-I (Chm-I). Therefore, the purpose of this study was to illustrate whether Chm-I was indispensable for stable ectopic chondrogenesis by chondrocyte, which may help to solve the problem of MSC ectopic ossification in the future. The current study demonstrated that Chm-I knockout did not obviously influence articular cartilage development in situ. However, native articular cartilage from Chm-I knockout (Chm-I(-/-), KO), but not wild-type (WT) mice, showed obvious ossification after subcutaneously implanted into nude mice for 16 days. Interestingly, cell morphology, cartilage-specific matrix expression, and pellet culture demonstrated that Chm-I knockout had no obvious influence on the phenotype, function, and chondrogenic ability of chondrocytes in vitro, except that cells in the WT group proliferated a little faster than those in the KO group. Nevertheless, Chm-I knockout directly interfered with in vivo ectopic cartilage regeneration when chondrocytes were subcutaneously injected into nude mice with matrigel. Moreover, Chm-I knockout obviously compromised ectopic stability of in vitro regenerated cartilage after subcutaneous implantation. These findings indicated that Chm-I was an indispensable factor for ectopic cartilage regeneration and the maintenance of cartilage homeostasis, which may provide a clue for solving the stability problem of MSC regenerated cartilage in ectopic niche. In addition, this study also provides a novel model based on tissue engineering strategy to properly evaluate the function of other targeted genes.