title: β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions.
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 β1 integrin blocking antibody. In conclusion, our data suggest that attachment of MSC to ex vivo full-thickness cartilage lesions is almost entirely β1 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.
authors: Department of Biomedical Sciences, University of Veterinary Medicine , Vienna, Austria .
authors: Daniela
authors: D
authors: Zwolanek
authors: Department of Biomedical Sciences, University of Veterinary Medicine , Vienna, Austria .
authors: Magdalena
authors: M
authors: Flicker
authors: Department of Biomedical Sciences, University of Veterinary Medicine , Vienna, Austria .
authors: Elisabeth
authors: E
authors: Kirstätter
authors: Center for Biochemistry and Cologne Center for Musculoskeletal Biomechanics, Medical Faculty, University of Cologne , Cologne, Germany .
authors: Frank
authors: F
authors: Zaucke
authors: Department of Orthopaedics and Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam , Rotterdam, The Netherlands .
authors: Gerjo J V M
authors: GJ
authors: van Osch
authors: Department of Biomedical Sciences, University of Veterinary Medicine , Vienna, Austria .
authors: Reinhold G
authors: RG
authors: Erben
keywords: biochemistry; cellular biology; extracellular matrix; stem cells