CYR61/CCN1 and WISP3/CCN6 are chemoattractive ligands for human multipotent mesenchymal stroma cells.
BACKGROUND
CCN-proteins are known to be involved in development, homeostasis and repair of mesenchymal tissues. Since these processes implicate recruitment of cells with the potential to be committed to various phenotypes, we studied the effect of CYR61/CCN1 and WISP3/CCN6 on migration of human bone marrow derived mesenchymal stroma cells (MSCs) in comparison to in vitro osteogenic differentiated MSCs using a modified Boyden chamber assay.


RESULTS
CYR61 and WISP3 were purified as fusion proteins with a C-terminal Fc-tag from baculovirus infected SF21 cells using protein G sepharose columns. CYR61 and WISP3 stimulated cell migration of undifferentiated MSCs in a dose-dependent manner. CYR61 and WISP3 had similar effects on committed osteogenic precursor cells. Checkerboard analysis revealed that CYR61 and WISP3 stimulated true directed cell migration (chemotaxis) of MSCs and committed osteogenic precursors. In MSCs the chemotactic activity of WISP3 but not CYR61 was mediated through integrin alphanuss5.


CONCLUSIONS
Our results indicate that CYR61 and WISP3 can function as soluble ligands transmitting chemotactic signals to human MSCs but differ in the involvement of integrin alphanuss5. This may be relevant for their possible role in connective tissue repair.
Schütze
Norbert
N
Orthopedic Department, Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany. rolf.brenner@uni-ulm.de.
Schenk
Rita
R
Fiedler
Jörg
J
Mattes
Thomas
T
Jakob
Franz
F
Brenner
Rolf E
RE
D000328:Adult; D055511:CCN Intercellular Signaling Proteins; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D055515:Cysteine-Rich Protein 61; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction
D055511:CCN Intercellular Signaling Proteins; C501848:CCN1 protein, human; C400081:CCN6 protein, human; D002630:Chemotactic Factors; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins