Short-term response of primary human meniscus cells to simulated microgravity.
Knee osteoarthritis
Primary cells
RNA-seq
Sex characteristics
Tissue engineering
Weightlessness simulation
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
21 Jun 2024
21 Jun 2024
Historique:
received:
22
02
2024
accepted:
27
05
2024
medline:
22
6
2024
pubmed:
22
6
2024
entrez:
21
6
2024
Statut:
epublish
Résumé
Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events. In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture. RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes. These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets.
Sections du résumé
BACKGROUND
BACKGROUND
Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events.
METHODS
METHODS
In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture.
RESULTS
RESULTS
RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes.
CONCLUSION
CONCLUSIONS
These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets.
Identifiants
pubmed: 38907358
doi: 10.1186/s12964-024-01684-w
pii: 10.1186/s12964-024-01684-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
342Subventions
Organisme : Women and Children's Health Research Institute
ID : Graduate Studentship
Organisme : Women and Children's Health Research Institute
ID : UOFAB WCHRIIG 3126 Adesida
Organisme : Women and Children's Health Research Institute
ID : UOFAB WCHRIIG 3126 Adesida
Organisme : Canadian Space Agency
ID : CSA FAST 21FAALBA04
Organisme : Canadian Space Agency
ID : CSA FAST 21FAALBA04
Organisme : Canadian Space Agency
ID : CSA FAST 21FAALBA04
Organisme : Canadian Space Agency
ID : CSA FAST 21FAALBA04
Organisme : Canadian Space Agency
ID : CSA FAST 21FAALBA04
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : NSERC RGPIN-2018-06290 Adesida
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : NSERC RGPIN-2018-06290 Adesida
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : NSERC RGPIN-2018-06290 Adesida
Organisme : Natural Sciences and Engineering Research Council of Canada
ID : NSERC RGPIN-2018-06290 Adesida
Organisme : University Hospital Foundation
ID : RES00045921 Adesida
Informations de copyright
© 2024. The Author(s).
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