Search: onr:"swepub:oai:DiVA.org:uu-307869" >
Chondrocytes Derive...
Chondrocytes Derived From Mesenchymal Stromal Cells and Induced Pluripotent Cells of Patients With Familial Osteochondritis Dissecans Exhibit an Endoplasmic Reticulum Stress Response and Defective Matrix Assembly
-
- Xu, Maojia (author)
- Natl Univ Ireland Galway, Sch Med, Regenerat Med Inst, Galway, Ireland.,National University of Ireland Galway
-
- Stattin, Eva-Lena (author)
- Uppsala University,Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
-
- Shaw, Georgina (author)
- Natl Univ Ireland Galway, Sch Med, Regenerat Med Inst, Galway, Ireland.,National University of Ireland Galway
-
show more...
-
- Heinegård, Dick (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
-
- Sullivan, Gareth (author)
- Norwegian Ctr Stem Cell Res, Oslo, Norway.,Norwegian Center for Stem Cell Research
-
- Wilmut, Ian (author)
- Univ Edinburgh, MRC, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland.,University of Edinburgh
-
- Colman, Alan (author)
- A STAR Inst Med Biol, Singapore, Singapore.,A*STAR Institute of Medical Biology (IMB)
-
- Önnerfjord, Patrik (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
-
- Khabut, Areej (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
-
- Aspberg, Anders (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
-
- Dockery, Peter (author)
- Natl Univ Ireland Galway, Sch Med, Dept Anat, Galway, Ireland.,National University of Ireland Galway
-
- Hardingham, Timothy (author)
- Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester, Lancs, England.,University of Manchester
-
- Murphy, Mary (author)
- Natl Univ Ireland Galway, Sch Med, Regenerat Med Inst, Galway, Ireland.,National University of Ireland Galway
-
- Barry, Frank (author)
- Natl Univ Ireland Galway, Sch Med, Regenerat Med Inst, Galway, Ireland.,National University of Ireland Galway
-
show less...
-
Natl Univ Ireland Galway, Sch Med, Regenerat Med Inst, Galway, Ireland National University of Ireland Galway (creator_code:org_t)
- 2016-07-07
- 2016
- English.
-
In: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 5:9, s. 1171-1181
- Related links:
-
https://doi.org/10.5...
-
show more...
-
http://dx.doi.org/10...
-
https://urn.kb.se/re...
-
https://doi.org/10.5...
-
https://lup.lub.lu.s...
-
show less...
Abstract
Subject headings
Close
- Familial osteochondritis dissecans (FOCD) is an inherited skeletal defect characterized by the development of large cartilage lesions in multiple joints, short stature, and early onset of severe osteoarthritis. It is associated with a heterozygous mutation in the ACAN gene, resulting in a Val-Met replacement in the C-type lectin domain of aggrecan. To understand the cellular pathogenesis of this condition, we studied the chondrogenic differentiation of patient bone marrow mesenchymal stromal cells (BM-MSCs). We also looked at cartilage derived from induced pluripotent stem cells (iPSCs) generated from patient fibroblasts. Our results revealed several characteristics of the differentiated chondrocytes that help to explain the disease phenotype and susceptibility to cartilage injury. First, patient chondrogenic pellets had poor structural integrity but were rich in glycosaminoglycan. Second, it was evident that large amounts of aggrecan accumulated within the endoplasmic reticulum of chondrocytes differentiated from both BM-MSCs and iPSCs. In turn, there was a marked absence of aggrecan in the extracellular matrix. Third, it was evident that matrix synthesis and assembly were globally dysregulated. These results highlight some of the abnormal aspects of chondrogenesis in these patient cells and help to explain the underlying cellular pathology. The results suggest that FOCD is a chondrocyte aggrecanosis with associated matrix dysregulation. The work provides a new in vitro model of osteoarthritis and cartilage degeneration based on the use of iPSCs and highlights how insights into disease phenotype and pathogenesis can be uncovered by studying differentiation of patient stem cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Osteoarthritis
- Familial osteochondritis dissecans
- Mesenchymal stromal cells
- Induced pluripotent stem cells
- Stem cell disease models
- Cellular pathology
- Aggrecan mutation
- Endoplasmic reticulum stress
- Aggrecan mutation
- Cellular pathology
- Endoplasmic reticulum stress
- Familial osteochondritis dissecans
- Induced pluripotent stem cells
- Mesenchymal stromal cells
- Osteoarthritis
- Stem cell disease models
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Xu, Maojia
-
Stattin, Eva-Len ...
-
Shaw, Georgina
-
Heinegård, Dick
-
Sullivan, Gareth
-
Wilmut, Ian
-
show more...
-
Colman, Alan
-
Önnerfjord, Patr ...
-
Khabut, Areej
-
Aspberg, Anders
-
Dockery, Peter
-
Hardingham, Timo ...
-
Murphy, Mary
-
Barry, Frank
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Cell and Molecul ...
- Articles in the publication
-
Stem Cells Trans ...
- By the university
-
Uppsala University
-
Lund University