Joint morphogenetic cells in the adult mammalian synovium

Anke J Roelofs; Janja Zupan; Anna H. K. Riemen; Karolina Kania; Sharon Ansboro; Nathan White; Susan M Clark; Cosimo De Bari

doi:10.1038/ncomms15040

Joint morphogenetic cells in the adult mammalian synovium

Anke J Roelofs, Janja Zupan, Anna H. K. Riemen, Karolina Kania, Sharon Ansboro, Nathan White, Susan M Clark, Cosimo De Bari^* (Corresponding Author)

^*Corresponding author for this work

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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 language	English
Article number	15040
Number of pages	14
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15040
Publication status	Published - 16 May 2017

Bibliographical 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).

Keywords

cartilage
mesenchymal stem cells
stem-cell research

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Joint morphogenetic cells in the adult mammalian synovium
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Cosimo De Bari
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Clinical Chair in Experimental Medicine and Rheumatology
- School of Medicine, Medical Sciences & Nutrition, Molecular and Cellular Function
- School of Medicine, Medical Sciences & Nutrition, MRC/Versus Arthritis Centre for Musculoskeletal Health and Work
- Institute of Medical Sciences
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Arthritis and Musculoskeletal Health (ACAMH)
Person: Clinical Academic
Anke Roelofs
Person: Academic

Iain Fraser Cytometry Centre
Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)
Institute of Medical Sciences
Research Facilities: Facility

Cite this

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title = "Joint morphogenetic cells in the adult mammalian synovium",

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{\textquoteright}Accio and Frank Luyten for support and helpful discussions; Staff at the University of Aberdeen{\textquoteright}s Animal Facility, Microscopy & Histology Facility and Iain Fraser Cytometry Centre for their support. C.D.B. is grateful to Dr Frank Luyten{\textquoteright}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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AU - Zupan, Janja

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AU - Ansboro, Sharon

AU - White, Nathan

AU - Clark, Susan M

AU - De Bari, Cosimo

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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.

AB - 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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JO - Nature Communications

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ER -

Joint morphogenetic cells in the adult mammalian synovium

Abstract

Bibliographical note

Keywords

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Cosimo De Bari

Anke Roelofs

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Iain Fraser Cytometry Centre

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