Joint morphogenetic cells in the adult mammalian synovium

Anke J Roelofs, Janja Zupan, Anna Helene Katrin Riemen, Karolina Kania, Sharon Ansboro, Nathan White, Susan M Clark, Cosimo De Bari

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Abstract

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.
Original languageEnglish
Article number15040
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 16 May 2017

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Synovial Membrane
stem cells
Stem cells
Mesenchymal Stromal Cells
Joints
Stem Cells
cartilage
Cartilage
cells
Nestin
linings
Linings
Hyperplasia
Repair
Leptin Receptors
bone marrow
Wounds and Injuries
Chondrocytes
tracing
Ablation

Keywords

  • cartilage
  • mesenchymal stem cells
  • stem-cell research

Cite this

Joint morphogenetic cells in the adult mammalian synovium. / Roelofs, Anke J; Zupan, Janja; Riemen, Anna Helene Katrin; Kania, Karolina; Ansboro, Sharon; White, Nathan; Clark, Susan M; De Bari, Cosimo.

In: Nature Communications, Vol. 8, 15040 , 16.05.2017.

Research output: Contribution to journalArticle

Roelofs, Anke J ; Zupan, Janja ; Riemen, Anna Helene Katrin ; Kania, Karolina ; Ansboro, Sharon ; White, Nathan ; Clark, Susan M ; De Bari, Cosimo. / Joint morphogenetic cells in the adult mammalian synovium. In: Nature Communications. 2017 ; Vol. 8.
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abstract = "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.",
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note = "The authors thank all members of the Arthritis & Regenerative Medicine Laboratory, particularly Dr Ana Sergijenko; Drs David Kingsley, Grigori Enikolopov, Fernando Camargo and Lora Heisler for sharing transgenic mice; Drs Henning Wackerhage, Neil Vargesson, Lynda Erskine, Chris Buckley, Francesco Dell’Accio and Frank Luyten for support and helpful discussions; Staff at the University of Aberdeen’s Animal Facility, Microscopy & Histology Facility and Iain Fraser Cytometry Centre for their support. C.D.B. is grateful to Dr Frank Luyten’s support for the experiment in Fig. 8, performed in his laboratory at KU Leuven, Belgium. We are grateful for the following funding: Arthritis Research UK (Grants No. 20050, 19429 and 20775), Medical Research Council (Grant No. MR/L020211/1) and Tenovus Scotland (Grant No. G13/14). A.H.K.R. is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (Grant No. WT 085664).",
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N2 - 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.

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