Universität zu Köln

Zwolanek, Daniela, Flicker, Magdalena, Kirstaetter, Elisabeth, Zaucke, Frank, van Osch, Gerjo J. V. M. and Erben, Reinhold G. (2015). beta 1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions. BioResearch Open Access, 4 (1). S. 39 - 54. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 2164-7860

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Abstract

Mesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC attachment to defective articular cartilage. Here, we developed an ex vivo attachment system, using rat osteochondral explants with artificially created full-thickness cartilage defects in combination with genetically labeled MSC isolated from bone marrow of human placental alkaline phosphatase transgenic rats. Binding of MSC to full-thickness cartilage lesions was improved by serum, but not hyaluronic acid, and was dependent on the presence of divalent cations. Additional in vitro tests showed that rat MSC attach, in a divalent cation-dependent manner, to collagen I, collagen II, and fibronectin, but not to collagen XXII or cartilage oligomeric matrix protein (COMP). RGD peptides partially blocked the adhesion of MSC to fibronectin in vitro and to cartilage lesions ex vivo. Furthermore, the attachment of MSC to collagen I and II in vitro and to cartilage lesions ex vivo was almost completely abolished in the presence of a beta 1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness cartilage lesions is almost entirely beta 1 integrin-mediated, whereby both RGD-and collagen-binding integrins are involved. These findings suggest a key role of integrins during MSC attachment to defective cartilage and may pave the way for improved MSC-based therapies in the future.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zwolanek, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Flicker, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirstaetter, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED van Osch, Gerjo J. V. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erben, Reinhold G. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-399397
DOI:	10.1089/biores.2014.0055
Journal or Publication Title:	BioResearch Open Access
Volume:	4
Number:	1
Page Range:	S. 39 - 54
Date:	2015
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	2164-7860
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRAARTICULAR INJECTION; ALKALINE-PHOSPHATASE; INTEGRIN EXPRESSION; ARTICULAR-CARTILAGE; COLLAGEN XXII; BINDING-SITE; BONE; OSTEOARTHRITIS; THERAPY; MARKER Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39939