Identification of the skeletal progenitor cells forming osteophytes in osteoarthritis.
Identification of the skeletal progenitor cells forming osteophytes in osteoarthritis.
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DOI：
10.1136/annrheumdis-2020-218350
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发表时间：
2020-12
影响因子：
27.4
通讯作者：
De Bari C
中科院分区：
文献类型：
--
作者：
Roelofs AJ;Kania K;Rafipay AJ;Sambale M;Kuwahara ST;Collins FL;Smeeton J;Serowoky MA;Rowley L;Wang H;Gronewold R;Kapeni C;Méndez-Ferrer S;Little CB;Bateman JF;Pap T;Mariani FV;Sherwood J;Crump JG;De Bari C
骨赘在骨关节炎（OA）中非常普遍，并与疼痛和功能障碍相关。软骨和骨的这些病理性增生通常形成于关节软骨、骨膜和滑膜的连接处。本研究的目的是鉴定OA中形成骨赘的细胞。荧光遗传细胞标记和跟踪小鼠模型诱导与他莫昔芬开关报告表达，适当的话，然后通过手术诱导内侧半月板的不稳定。荧光标记的细胞骨赘后2或8周，其分子身份的贡献，进行了分析，组织学，免疫荧光染色和RNA原位杂交。使用与多色Confetti报告小鼠杂交的Pdgfrα-H2 BGFP小鼠和Pdgfrα-CreER小鼠用于间充质祖细胞的鉴定和克隆追踪。将携带Col 2-CreER、Nes-CreER、LepR-Cre、Grem 1-CreER、Gdf 5-Cre、Sox 9-CreER或Prg 4-CreER的小鼠与tdTomato报告小鼠杂交，以谱系示踪软骨细胞和干/祖细胞亚群。通过内斯、LepR或Grem 1表达鉴定的关节软骨细胞或骨骼干细胞没有产生骨赘。相反，骨赘来源于骨膜和滑膜中表达Pdgfrα的干/祖细胞，这些干/祖细胞是表达Gdf 5的胚胎关节间区的后代。此外，我们发现，Sox 9表达的祖细胞在骨膜提供的混合骨骼细胞的早期骨赘，而Prg 4表达的祖细胞从滑膜衬里有助于软骨覆盖骨赘，但不是骨。我们的研究结果揭示了不同的骨膜和滑膜骨骼祖细胞合作，形成骨赘在OA。这些细胞群可以在用于治疗OA的疾病修饰中被靶向。
Osteophytes are highly prevalent in osteoarthritis (OA) and are associated with pain and functional disability. These pathological outgrowths of cartilage and bone typically form at the junction of articular cartilage, periosteum and synovium. The aim of this study was to identify the cells forming osteophytes in OA. Fluorescent genetic cell-labelling and tracing mouse models were induced with tamoxifen to switch on reporter expression, as appropriate, followed by surgery to induce destabilisation of the medial meniscus. Contributions of fluorescently labelled cells to osteophytes after 2 or 8 weeks, and their molecular identity, were analysed by histology, immunofluorescence staining and RNA in situ hybridisation. Pdgfrα-H2BGFP mice and Pdgfrα-CreER mice crossed with multicolour Confetti reporter mice were used for identification and clonal tracing of mesenchymal progenitors. Mice carrying Col2-CreER, Nes-CreER, LepR-Cre, Grem1-CreER, Gdf5-Cre, Sox9-CreER or Prg4-CreER were crossed with tdTomato reporter mice to lineage-trace chondrocytes and stem/progenitor cell subpopulations. Articular chondrocytes, or skeletal stem cells identified by Nes, LepR or Grem1 expression, did not give rise to osteophytes. Instead, osteophytes derived from Pdgfrα-expressing stem/progenitor cells in periosteum and synovium that are descendants from the Gdf5-expressing embryonic joint interzone. Further, we show that Sox9-expressing progenitors in periosteum supplied hybrid skeletal cells to the early osteophyte, while Prg4-expressing progenitors from synovial lining contributed to cartilage capping the osteophyte, but not to bone. Our findings reveal distinct periosteal and synovial skeletal progenitors that cooperate to form osteophytes in OA. These cell populations could be targeted in disease modification for treatment of OA.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
7.7
作者：
Isern J;García-García A;Martín AM;Arranz L;Martín-Pérez D;Torroja C;Sánchez-Cabo F;Méndez-Ferrer S
通讯作者：
Méndez-Ferrer S
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
小鼠骨髓中多能间充质干细胞的前瞻性鉴定、分离和系统移植。
DOI：
10.1084/jem.20091046
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Morikawa S;Mabuchi Y;Kubota Y;Nagai Y;Niibe K;Hiratsu E;Suzuki S;Miyauchi-Hara C;Nagoshi N;Sunabori T;Shimmura S;Miyawaki A;Nakagawa T;Suda T;Okano H;Matsuzaki Y
通讯作者：
Matsuzaki Y
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H