Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury

Ana Sergijenko; Anke J. Roelofs; Anna H. K. Riemen; Cosimo De Bari

doi:10.1186/s13075-016-1060-8

Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury

Ana Sergijenko, Anke J. Roelofs, Anna H. K. Riemen, Cosimo De Bari^* (Corresponding Author)

^*Corresponding author for this work

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Abstract

Background
Joint surface injury, a known risk factor for osteoarthritis, triggers synovial hyperplasia, which involves proliferation of mesenchymal stromal/stem cells (MSCs). Whether these proliferative MSCs are resident synovial cells or move into the tissue from elsewhere is not known. The aim of this study was to determine the contribution of bone marrow-derived cells to synovial hyperplasia following joint surface injury.

Methods
Lethally irradiated mice were transplanted with green fluorescent protein (GFP)-labelled bone marrow, and MSC chimerism was determined by the colony-forming unit fibroblast (CFU-F) assay and phenotypic analysis. To label host slow-cycling cells prior to bone marrow transplant, mice received iododeoxyuridine for 3 weeks. Mice then were subjected to GFP+ bone marrow transplant, underwent joint surface injury and received chlorodeoxyuridine (CldU) for 7 days to label cells proliferating after injury. GFP- and nucleoside-labelled cells in normal and injured knee joint synovium were quantified in situ by immunofluorescence staining of paraffin-embedded tissue sections. The phenotype of GFP-labelled cells was determined by co-staining for the haematopoietic marker CD16/CD32 and the MSC/fibroblast marker platelet-derived growth factor receptor α (Pdgfrα).

Results
CFU-F assay and phenotypic analysis demonstrated successful bone marrow mesenchymal lineage chimerism in mice that underwent transplants. Bone marrow reconstitution preceded the detection of GFP-labelled cells in synovium. The percentage of GFP+ cells in synovium increased significantly in response to injury, while the proportion of GFP+ cells that were labelled with the proliferation marker CldU did not increase, suggesting that the expansion of the GFP+ cell population in synovium was due mainly to bone marrow cell infiltration. In contrast, proliferation of host slow-cycling cells was significantly increased in the hyperplastic synovium. In both control and injured knee joints, the majority of marrow-derived GFP+ cells in the synovium were haematopoietic (CD16/32+), while a minority of cells expressed the pan-fibroblast/MSC marker Pdgfrα.

Conclusions
Our findings indicate that synovial hyperplasia following joint surface injury involves proliferation of resident slow-cycling cells, with a contribution from infiltrating bone marrow-derived cells. Understanding the process of synovial hyperplasia may reveal ways to restore homeostasis in injured joints and prevent secondary osteoarthritis.

Original language	English
Article number	166
Number of pages	11
Journal	Arthritis Research & Therapy
Volume	18
DOIs	https://doi.org/10.1186/s13075-016-1060-8
Publication status	Published - 13 Jul 2016

Bibliographical note

Acknowledgements

We thank Dr. Andrea Augello and Dr. Donna MacCallum for advice and help with animal procedures, Susan Clark and Denise Tosh for general technical help and support, and the Arthritis and Regenerative Medicine Laboratory and Arthritis and Musculoskeletal Medicine Programme for general support and scientific discussions. We acknowledge the Iain Fraser Cytometry Centre, the animal facility staff and the Microscopy and Histology Facility, in particular Kevin Mackenzie, Gillian Milne and Lucy Wight for their support. This work was supported by Arthritis Research UK (grants 19271, 19429 and 20050). AHKR is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (grant WT 085664).

Keywords

mesenchymal stem cells
stromal cells
synovium
bone marrow transplantation
joint injury

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Bone marrow contribution to synovial hyperplasia following joint surface injury
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Cite this

@article{aa0de940cfff4a79a30357c78d6b5255,

title = "Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury",

abstract = "BackgroundJoint surface injury, a known risk factor for osteoarthritis, triggers synovial hyperplasia, which involves proliferation of mesenchymal stromal/stem cells (MSCs). Whether these proliferative MSCs are resident synovial cells or move into the tissue from elsewhere is not known. The aim of this study was to determine the contribution of bone marrow-derived cells to synovial hyperplasia following joint surface injury.MethodsLethally irradiated mice were transplanted with green fluorescent protein (GFP)-labelled bone marrow, and MSC chimerism was determined by the colony-forming unit fibroblast (CFU-F) assay and phenotypic analysis. To label host slow-cycling cells prior to bone marrow transplant, mice received iododeoxyuridine for 3 weeks. Mice then were subjected to GFP+ bone marrow transplant, underwent joint surface injury and received chlorodeoxyuridine (CldU) for 7 days to label cells proliferating after injury. GFP- and nucleoside-labelled cells in normal and injured knee joint synovium were quantified in situ by immunofluorescence staining of paraffin-embedded tissue sections. The phenotype of GFP-labelled cells was determined by co-staining for the haematopoietic marker CD16/CD32 and the MSC/fibroblast marker platelet-derived growth factor receptor α (Pdgfrα).ResultsCFU-F assay and phenotypic analysis demonstrated successful bone marrow mesenchymal lineage chimerism in mice that underwent transplants. Bone marrow reconstitution preceded the detection of GFP-labelled cells in synovium. The percentage of GFP+ cells in synovium increased significantly in response to injury, while the proportion of GFP+ cells that were labelled with the proliferation marker CldU did not increase, suggesting that the expansion of the GFP+ cell population in synovium was due mainly to bone marrow cell infiltration. In contrast, proliferation of host slow-cycling cells was significantly increased in the hyperplastic synovium. In both control and injured knee joints, the majority of marrow-derived GFP+ cells in the synovium were haematopoietic (CD16/32+), while a minority of cells expressed the pan-fibroblast/MSC marker Pdgfrα.ConclusionsOur findings indicate that synovial hyperplasia following joint surface injury involves proliferation of resident slow-cycling cells, with a contribution from infiltrating bone marrow-derived cells. Understanding the process of synovial hyperplasia may reveal ways to restore homeostasis in injured joints and prevent secondary osteoarthritis.",

keywords = "mesenchymal stem cells, stromal cells, synovium, bone marrow transplantation, joint injury",

author = "Ana Sergijenko and Roelofs, {Anke J.} and Riemen, {Anna H. K.} and {De Bari}, Cosimo",

note = "Acknowledgements We thank Dr. Andrea Augello and Dr. Donna MacCallum for advice and help with animal procedures, Susan Clark and Denise Tosh for general technical help and support, and the Arthritis and Regenerative Medicine Laboratory and Arthritis and Musculoskeletal Medicine Programme for general support and scientific discussions. We acknowledge the Iain Fraser Cytometry Centre, the animal facility staff and the Microscopy and Histology Facility, in particular Kevin Mackenzie, Gillian Milne and Lucy Wight for their support. This work was supported by Arthritis Research UK (grants 19271, 19429 and 20050). AHKR is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (grant WT 085664).",

year = "2016",

month = jul,

day = "13",

doi = "10.1186/s13075-016-1060-8",

language = "English",

volume = "18",

journal = "Arthritis Research & Therapy",

issn = "1478-6354",

publisher = "BioMed Central",

}

TY - JOUR

T1 - Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury

AU - Sergijenko, Ana

AU - Roelofs, Anke J.

AU - Riemen, Anna H. K.

AU - De Bari, Cosimo

N1 - Acknowledgements We thank Dr. Andrea Augello and Dr. Donna MacCallum for advice and help with animal procedures, Susan Clark and Denise Tosh for general technical help and support, and the Arthritis and Regenerative Medicine Laboratory and Arthritis and Musculoskeletal Medicine Programme for general support and scientific discussions. We acknowledge the Iain Fraser Cytometry Centre, the animal facility staff and the Microscopy and Histology Facility, in particular Kevin Mackenzie, Gillian Milne and Lucy Wight for their support. This work was supported by Arthritis Research UK (grants 19271, 19429 and 20050). AHKR is supported by the Wellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative (grant WT 085664).

PY - 2016/7/13

Y1 - 2016/7/13

N2 - BackgroundJoint surface injury, a known risk factor for osteoarthritis, triggers synovial hyperplasia, which involves proliferation of mesenchymal stromal/stem cells (MSCs). Whether these proliferative MSCs are resident synovial cells or move into the tissue from elsewhere is not known. The aim of this study was to determine the contribution of bone marrow-derived cells to synovial hyperplasia following joint surface injury.MethodsLethally irradiated mice were transplanted with green fluorescent protein (GFP)-labelled bone marrow, and MSC chimerism was determined by the colony-forming unit fibroblast (CFU-F) assay and phenotypic analysis. To label host slow-cycling cells prior to bone marrow transplant, mice received iododeoxyuridine for 3 weeks. Mice then were subjected to GFP+ bone marrow transplant, underwent joint surface injury and received chlorodeoxyuridine (CldU) for 7 days to label cells proliferating after injury. GFP- and nucleoside-labelled cells in normal and injured knee joint synovium were quantified in situ by immunofluorescence staining of paraffin-embedded tissue sections. The phenotype of GFP-labelled cells was determined by co-staining for the haematopoietic marker CD16/CD32 and the MSC/fibroblast marker platelet-derived growth factor receptor α (Pdgfrα).ResultsCFU-F assay and phenotypic analysis demonstrated successful bone marrow mesenchymal lineage chimerism in mice that underwent transplants. Bone marrow reconstitution preceded the detection of GFP-labelled cells in synovium. The percentage of GFP+ cells in synovium increased significantly in response to injury, while the proportion of GFP+ cells that were labelled with the proliferation marker CldU did not increase, suggesting that the expansion of the GFP+ cell population in synovium was due mainly to bone marrow cell infiltration. In contrast, proliferation of host slow-cycling cells was significantly increased in the hyperplastic synovium. In both control and injured knee joints, the majority of marrow-derived GFP+ cells in the synovium were haematopoietic (CD16/32+), while a minority of cells expressed the pan-fibroblast/MSC marker Pdgfrα.ConclusionsOur findings indicate that synovial hyperplasia following joint surface injury involves proliferation of resident slow-cycling cells, with a contribution from infiltrating bone marrow-derived cells. Understanding the process of synovial hyperplasia may reveal ways to restore homeostasis in injured joints and prevent secondary osteoarthritis.

AB - BackgroundJoint surface injury, a known risk factor for osteoarthritis, triggers synovial hyperplasia, which involves proliferation of mesenchymal stromal/stem cells (MSCs). Whether these proliferative MSCs are resident synovial cells or move into the tissue from elsewhere is not known. The aim of this study was to determine the contribution of bone marrow-derived cells to synovial hyperplasia following joint surface injury.MethodsLethally irradiated mice were transplanted with green fluorescent protein (GFP)-labelled bone marrow, and MSC chimerism was determined by the colony-forming unit fibroblast (CFU-F) assay and phenotypic analysis. To label host slow-cycling cells prior to bone marrow transplant, mice received iododeoxyuridine for 3 weeks. Mice then were subjected to GFP+ bone marrow transplant, underwent joint surface injury and received chlorodeoxyuridine (CldU) for 7 days to label cells proliferating after injury. GFP- and nucleoside-labelled cells in normal and injured knee joint synovium were quantified in situ by immunofluorescence staining of paraffin-embedded tissue sections. The phenotype of GFP-labelled cells was determined by co-staining for the haematopoietic marker CD16/CD32 and the MSC/fibroblast marker platelet-derived growth factor receptor α (Pdgfrα).ResultsCFU-F assay and phenotypic analysis demonstrated successful bone marrow mesenchymal lineage chimerism in mice that underwent transplants. Bone marrow reconstitution preceded the detection of GFP-labelled cells in synovium. The percentage of GFP+ cells in synovium increased significantly in response to injury, while the proportion of GFP+ cells that were labelled with the proliferation marker CldU did not increase, suggesting that the expansion of the GFP+ cell population in synovium was due mainly to bone marrow cell infiltration. In contrast, proliferation of host slow-cycling cells was significantly increased in the hyperplastic synovium. In both control and injured knee joints, the majority of marrow-derived GFP+ cells in the synovium were haematopoietic (CD16/32+), while a minority of cells expressed the pan-fibroblast/MSC marker Pdgfrα.ConclusionsOur findings indicate that synovial hyperplasia following joint surface injury involves proliferation of resident slow-cycling cells, with a contribution from infiltrating bone marrow-derived cells. Understanding the process of synovial hyperplasia may reveal ways to restore homeostasis in injured joints and prevent secondary osteoarthritis.

KW - mesenchymal stem cells

KW - stromal cells

KW - synovium

KW - bone marrow transplantation

KW - joint injury

U2 - 10.1186/s13075-016-1060-8

DO - 10.1186/s13075-016-1060-8

M3 - Article

SN - 1478-6354

VL - 18

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

M1 - 166

ER -

Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury

Abstract

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Cosimo De Bari

Anke Roelofs

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Bone Marrow Contribution to Synovial Hyperplasia Following Joint Surface Injury

Abstract

Bibliographical note

Keywords

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Cosimo De Bari

Anke Roelofs

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