Joint morphogenetic cells in the adult mammalian synovium.
Joint morphogenetic cells in the adult mammalian synovium.
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DOI：
10.1038/ncomms15040
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发表时间：
2017-05-16
影响因子：
16.6
通讯作者：
De Bari C
中科院分区：
文献类型：
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作者：
Roelofs AJ;Zupan J;Riemen AHK;Kania K;Ansboro S;White N;Clark SM;De Bari C
成年期保护滑膜关节的干细胞尚不清楚。间充质基质/干细胞（MSC）的研究主要集中在骨髓。在这里，我们展示了表达 Gdf5 的关节间细胞的谱系追踪，在成年小鼠滑膜中鉴定出骨骼干细胞标记物 Nestin-GFP、瘦素受体和 Gremlin1 基本上呈阴性的 MSC 群体。软骨损伤后，Gdf5 谱系细胞通过增殖支撑滑膜增生，被招募到血管周围的 Nestin-GFP 高群体中，并有助于软骨修复。转录辅因子 Yap 在损伤后上调，其在 Gdf5 谱系细胞中的条件性消融可防止滑膜内层增生并减少 Gdf5 谱系细胞对软骨修复的贡献。培养的 Gdf5 谱系细胞表现出稳定软骨细胞的祖细胞活性，并且能够三维自组织形成滑膜内衬样层。最后，用 Bmp7 转导的人类滑膜 MSC 通过在体内形成关节样器官的图案而显示出形态发生特性。我们的研究结果进一步加深了对成人骨骼干/祖细胞的了解。维持和修复哺乳动物成体关节组织（包括关节软骨）的干细胞仍未完全确定。在这里，作者在成年小鼠中进行了谱系追踪研究，发现了一种个体发育定义的祖细胞群，该祖细胞群在滑膜关节中具有功能，并且与之前报道的间充质干细胞群不同。
The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFPhigh perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life. The stem cells that maintain and repair adult joint tissues in mammals, including articular cartilage, remain incompletely defined. Here the authors perform lineage tracing studies in adult mice and find an ontogenetically defined progenitor cell population that is functional in the synovial joint and distinct from previously reported mesenchymal stem cell populations.