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Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

ABSTRACT: Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

PROVIDER: PRJNA702277 | ENA |

REPOSITORIES: ENA

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Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

Project description:This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human MFCs on a collagen scaffold were stimulated to form fibrocartilage over 6weeks under normoxic (NRX, 20% O2) conditions with supplemented TGF -β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O2) and then 5min of dynamic compression (DC) between 30 and 40% strain. Delayed HYP induced an anabolic and anti-catabolic expression profile for hyaline cartilage matrix markers, while DC induced an inflammatory matrix remodeling response along with upregulation of both SOX9 and COL1A1. There were 41 genes regulated by both HYP and DC. Overall, the combined treatment supported a unique gene expression profile favouring the hyaline cartilage aspect of inner meniscus matrix and matrix remodeling.

2021-02-17 | GSE166908 | GEO

Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression.

Project description: Not available

| S-EPMC7874349 | biostudies-literature

Effect of dynamic compression on meniscus tissue explants in the presence and absence of IL-1

Project description:Meniscus injuries are highly prevalent and are linked to the development of post-traumatic osteoarthritis (PTOA). The inflammatory cytokine IL-1 is elevated in synovial fluid following knee injuries, causes degradation of meniscus tissue, and inhibits meniscus repair. Dynamic mechanical compression of meniscus tissue has been shown to improve integrative repair in the presence of IL-1; however, there remains a dearth of knowledge on global effects of loading on meniscus cell phenotype and transcriptomic profiles. In this study, we performed mRNA-Seq on meniscus tissue explants from inner and outer zone regions of porcine menisci subjected to dynamic compression in the presence and absence of IL-1 to identify cellular responses to mechanical load, identify differences in response to load based on zonal characteristics, and identify IL-1 induced inflammatory responses modulated by load.

2021-12-24 | GSE191175 | GEO

Mechano-Hypoxia Conditioning of Engineered Human Meniscus

Project description:Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee, conditions that have promising applications in human meniscus tissue engineering. We hypothesized that “mechano-hypoxia conditioning,” using mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP), would enhance development of human meniscus fibrocartilage extracellular matrix in vitro. MFCs from inner human meniscus surgical discards were pre-cultured on porous type I collagen scaffolds with TGF-β3 supplementation to form baseline tissues with newly-formed matrix. They were then treated with DC or CHP under hypoxia (HYP, 3% O2) for 5 days. DC was the more effective load regime, and combined HYP/DC enhanced gene expression of fibrocartilage precursors. The individual treatments of DC and HYP regulated thousands of genes and combined in an overwhelmingly additive rather than synergistic manner. Baseline tissues were then treated with a short course of DC (5 vs 60 minutes, 10-20% vs 30-40% strain) with different pre-culture durations (3 vs 6 weeks). Longer courses of loading had diminishing returns in terms of gene regulation. There was a dose-effect for higher DC strains, whereas outcomes were mixed for different MFC donors in pre-culture durations. Finally, baseline tissues were conditioned for 3 weeks with mechano-hypoxia conditioning to assess mechanical and protein-level outcomes. There were 1.8 to 5.1-fold gains in the dynamic modulus relative to baseline in HYP/DC, but matrix outcomes were equal or inferior to static controls. Long-term mechano-hypoxia conditioning was effective in suppressing hypertrophic markers (e.g., COL10A1 10-fold suppression vs static/normoxia). Applied appropriately, mechano-hypoxia conditioning can support meniscus fibrocartilage development in vitro and may be useful as a strategy for developing non-hypertrophic articular cartilage using mesenchymal stem cells.

2021-08-23 | GSE180467 | GEO

Mechano-Hypoxia Conditioning of Engineered Human Meniscus

Project description:Mechano-Hypoxia Conditioning of Engineered Human Meniscus

| PRJNA748371 | ENA

Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro

Project description:This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences

2022-01-26 | GSE192982 | GEO

Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity

Project description:Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity

| PRJNA794056 | ENA

Compressed and non-compressed tissue-engineered HS-deficient and WT cartilage

Project description:Murine primary rib-cage chondrocytes (mRCs) were isolated from E15.5 WT and HS-deficient Ext1gt/gt mice and expanded for 6-7 days. Tissue-engineered cartilage was generated by a 14-day chondrogenic culture of mRCs at 5×10^5 cells per 25 µl agarose carrier. Engineered cartilage was exposed to cyclic unconfined compression for 3 hours: 10-minute cycles of dynamic unconfined compression (25 % dynamic compression at 1 Hz superimposed to 10 % static off-set) were intermitted by 10-minute breaks (10 % static off-set).

2021-03-14 | E-MTAB-10258 | biostudies-arrayexpress

Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro

Project description:Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro

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Gene signature of the embryonic meniscus

Project description:Analysis of gene expression in E16 mouse meniscus, articular cartilage, and cruciate ligaments Limbs were dissected from E16 CD-1 mice. Samples were frozen in OCT and cryosectioned. Meniscus, articular carilage, and cruciate ligament were isolated using laser capture microdissection. Total RNA was isolated from these tissues, amplified, and gene expression was analyzed using microarrays. Three biological replicates were analyzed for each tissue type. Total RNA extracted from E16 mouse meniscus, articular cartilage, and cruciate ligaments

2013-10-01 | E-GEOD-47799 | biostudies-arrayexpress

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