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Transplanted Chondrocytes Inhibit Endochondral Ossification Within Cartilage Repair Tissue

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Abstract

The aim of this study was to investigate the effect of transplanted chondrocytes on endochondral bone formation in cartilage repair tissue. In the knee joint of miniature pigs, cartilage lesions were treated by microfracturing and were then either left empty, covered with a collagen membrane, or treated by matrix-associated autologous chondrocyte transplantation. In control lesions, the subchondral bone plate was left intact (partial-thickness lesion). The repair tissues were analyzed after 12 weeks by histological methods focusing on bone formation and vascularization. The effect of chondrocytes on angiogenesis was assessed by in vitro assays. The presence of antiangiogenic proteins in cartilage repair tissue, including thrombospondin-1 (TSP-1) and chondromodulin-I (ChM-I), was detected immunohistochemically and their expression in chondrocytes and bone marrow stromal cells was measured by quantitative RT-PCR. Significant outgrowths of subchondral bone and excessive endochondral ossification within the repair tissue were regularly observed in lesions with an exposed or microfractured subchondral bone plate. In contrast, such excessive bone formation was significantly inhibited by the additional transplantation of chondrocytes. Cartilaginous repair tissue that resisted ossification was strongly positive for the antiangiogenic proteins, TSP-1 and ChM-I, which were, however, not detectable in vascularized osseous outgrowths. Chondrocytes were identified to be the major source of TSP-1- and ChM-I expression and were shown to counteract the angiogenic activity of endothelial cells. These data suggest that the resistance of cartilaginous repair tissue against endochondral ossification following the transplantation of chondrocytes is associated with the presence of antiangiogenic proteins whose individual relevance has yet to be further explored.

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Acknowledgments

This study was supported by the Interdisciplinary Center of Clinical Research at the University of Erlangen (Grant C7), the German Research Foundation (Grant GE 1975/2-1), and the German Society of Orthopaedics and Orthopaedic Surgery (DGOOC, MSB-Net). We thank M. Gesslein and H. Rohrmueller for excellent technical assistance. Anti-ChM-I antibodies were generously provided by Y. Hiraki, Kyoto University, Japan.

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Authors and Affiliations

  1. Department of Orthopaedic Trauma Surgery, University Hospital Erlangen, Krankenhausstr. 12, 91054, Erlangen, Germany

    M. Blanke, P. Klinger, F. Hennig & K. Gelse

  2. Department of Orthopaedic Rheumatology, University of Erlangen-Nuremberg, Erlangen, Germany

    H. D. Carl, P. Klinger, B. Swoboda & K. Gelse

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  1. M. Blanke
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  2. H. D. Carl
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  4. B. Swoboda
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  6. K. Gelse
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Correspondence to K. Gelse.

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Blanke, M., Carl, H.D., Klinger, P. et al. Transplanted Chondrocytes Inhibit Endochondral Ossification Within Cartilage Repair Tissue. Calcif Tissue Int 85, 421–433 (2009). https://doi.org/10.1007/s00223-009-9288-9

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  • DOI: https://doi.org/10.1007/s00223-009-9288-9

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