Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10 and XCL1 recruit human subchondral mesenchymal progenitor cells.
OBJECTIVE
The microfracture technique activates mesenchymal progenitors that enter the cartilage defect and form cartilage repair tissue. Synovial fluid (SF) has been shown to stimulate the migration of subchondral progenitors. The aim of our study was to determine the chemokine profile of SF from normal, rheumatoid arthritis (RA) and osteoarthritis (OA) donors and evaluate the chemotactic effect of selected chemokines on human subchondral progenitor cells.


METHODS
Chemokine levels of SF were analyzed using human chemokine antibody membrane arrays. The chemotactic potential of selected chemokines on human mesenchymal progenitors derived from subchondral cortico-spongious bone was tested using 96-well chemotaxis assays. Chemokine receptor expression of subchondral progenitors was assessed by real-time gene expression analysis and immuno-histochemistry.


RESULTS
Chemokine antibody array analysis showed that SF contains a broad range of chemokines. Ten chemokines that showed significantly reduced levels in RA or OA compared to normal SF or robustly high levels in all SF tested were used for further chemotactic analysis. Chemotaxis assays showed that the chemokines MDC/CCL22, CTACK/CCL27, ENA78/CXCL5 and SDF1α/CXCL12 significantly inhibited migration of progenitors, while TECK/CCL25, IP10/CXCL10 and Lymphotactin/XCL1 effectively stimulated cell migration. MCP1/CCL2, Eotaxin2/CCL24 and NAP2/CXCL7 showed no chemotactic effect on subchondral progenitors. Gene expression and immuno-histochemical analysis of corresponding chemokine receptors document presence of low levels of chemokine receptors in subchondral progenitors, with the CXCL10 receptor CXCR3 showing the highest expression level.


CONCLUSIONS
These results suggest that SF contains chemokines that may contribute to the recruitment of human mesenchymal progenitors from the subchondral bone in microfracture.
Endres
M
M
TransTissue Technologies GmbH, Tucholskystrasse 2, 10117 Berlin, Germany.
Andreas
K
K
Kalwitz
G
G
Freymann
U
U
Neumann
K
K
Ringe
J
J
Sittinger
M
M
Häupl
T
T
Kaps
C
C
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D054443:Cell Migration Assays; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019744:Chemokines, C / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010003:Osteoarthritis / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology*
D015415:Biomarkers; C108074:CCL25 protein, human; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019744:Chemokines, C; D019742:Chemokines, CC; C092390:XCL1 protein, human