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Abstract
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) and induced pluripotent stem cells (iPSCs) from patients with familial osteochondritis dissecans (FOCD) were studied. Chondrogenic pellets had poor structural integrity but were rich in glycosaminoglycan. Large amounts of aggrecan accumulated within the endoplasmic reticulum of chondrocytes, with a marked absence of aggrecan in the extracellular matrix. Matrix synthesis and assembly were globally dysregulated. These results suggest that FOCD is a chondrocyte aggrecanosis with associated matrix dysregulation.
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Details
1 Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland
2 Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
3 Department of Clinical Sciences, Rheumatology, and Molecular Skeletal Biology, Lund University, Lund, Sweden
4 Norwegian Center for Stem Cell Research, Oslo, Norway
5 Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
6 A*STAR Institute of Medical Biology, Singapore
7 Anatomy, School of Medicine, National University of Ireland Galway, Galway, Ireland
8 Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences University of Manchester, Manchester, United Kingdom