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Chondrocytes Derived From Mesenchymal Stromal Cells and Induced Pluripotent Cells of Patients With Familial Osteochondritis Dissecans Exhibit an Endoplasmic Reticulum Stress Response and Defective…

Overview of attention for article published in Stem Cells Translational Medicine, July 2016
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Title
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
Published in
Stem Cells Translational Medicine, July 2016
DOI 10.5966/sctm.2015-0384
Pubmed ID
Authors

Maojia Xu, Eva-Lena Stattin, Georgina Shaw, Dick Heinegård, Gareth Sullivan, Ian Wilmut, Alan Colman, Patrik Önnerfjord, Areej Khabut, Anders Aspberg, Peter Dockery, Timothy Hardingham, Mary Murphy, Frank Barry

Abstract

: 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 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. The isolation and study of patient stem cells and the development of methods for the generation of iPSCs have opened up exciting opportunities in understanding causes and exploring new treatments for major diseases. This technology was used to unravel the cellular phenotype in a severe form of inherited osteoarthritis, termed familial osteochondritis dissecans. The phenotypic abnormalities that give rise to cartilage lesions in these patients were able to be described via the generation of chondrocytes from bone marrow-derived mesenchymal stromal cells and iPSCs, illustrating the extraordinary value of these approaches in disease modeling.

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 23%
Student > Ph. D. Student 5 16%
Researcher 4 13%
Student > Master 3 10%
Student > Postgraduate 2 6%
Other 3 10%
Unknown 7 23%
Readers by discipline Count As %
Medicine and Dentistry 10 32%
Biochemistry, Genetics and Molecular Biology 6 19%
Agricultural and Biological Sciences 3 10%
Engineering 2 6%
Nursing and Health Professions 1 3%
Other 1 3%
Unknown 8 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 July 2016.
All research outputs
#12,496,782
of 14,133,940 outputs
Outputs from Stem Cells Translational Medicine
#1,050
of 1,127 outputs
Outputs of similar age
#217,587
of 260,353 outputs
Outputs of similar age from Stem Cells Translational Medicine
#41
of 42 outputs
Altmetric has tracked 14,133,940 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,127 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.7. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 42 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.