Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity: A Transcriptomic Study

Ma, Zhiyao; Li, David Xinzheyang; Chee, Ryan K W; Kunze, Melanie; Mulet‐Sierra, Aillette; Sommerfeldt, Mark; Westover, Lindsey; Graf, Daniel; Adesida, Adetola B

doi:10.1038/s41597-022-01837-x

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…The other studies were conducted under conditions of s-µ g on devices such as the RCCS or the RPM. Ma et al [ 151 ] first generated engineered meniscus tissues by seeding meniscus fibrochondrocytes from female and male donors onto a cylindrical type 1 collagen scaffold and incubating them for two weeks in a TGF-b3-rich chondrogenic medium. The resulting meniscus models were then cultivated either as static controls or on an RCCS employing slow-turning lateral vessels for a further three weeks.…”

Section: Resultsmentioning

confidence: 99%

“…Female donors could be classified into low and high responders, while male donors remained in one group. Remarkably, genes related to osteoarthritis ( BMP8A , CD36 , COL10A1 , COL9A3 , FGF1 , IBSP , IHH , MMP10 , PHOSPHO1 , S100A1 , and SPP1 ) were significantly upregulated only in the female high-responder group, but not in the two others [ 151 ].…”

Section: Resultsmentioning

confidence: 99%

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Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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“…The utilization of real and simulated microgravity (SMG) has become a prominent tool for studying the effects of mechanical unloading on cartilage tissue at both the cellular and tissue levels [14][15][16]. In several studies, SMG was found to activate the Wnt-signaling pathway [14], leading to increased cartilage catabolism, reduced glycosaminoglycan (GAG) content, increased MMP3 and MMP13 expression, and an upregulation of cell apoptosis [17][18][19][20]. Although there are fewer investigations examining the effects of short-term microgravity culture compared to long-term culture, several studies using parabolic flight maneuvers demonstrated an acute adaptation of cellular activity to altered mechanical environments [21,22], but further research is necessary to elucidate the underlying mechanisms that govern the response of primary cells that are devoid of in vitro expansion culture on traditional tissue culture plastic.…”

Section: Introductionmentioning

confidence: 99%

Short-term response of primary human meniscus cells to simulated microgravity

Ma,

Li,

Lan

et al. 2024

Cell Commun Signal

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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 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 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 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.

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Meniscus gene expression profiling of inner and outer zone meniscus tissue compared to cartilage and passaged monolayer meniscus cells

Fei,

Andress,

Kelly

et al. 2024

Sci Rep

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Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue engineering are hindered by a lack of understanding of meniscus cell biology and a poorly defined meniscus cell phenotype. This study utilized bulk RNA-sequencing to identify unique and overlapping transcriptomic profiles in cartilage, inner and outer zone meniscus tissue, and passaged inner and outer zone meniscus cells. The greatest transcriptomic differences were identified when comparing meniscus tissue to passaged monolayer cells (> 4,600 differentially expressed genes (DEGs)) and meniscus tissue to cartilage (> 3,100 DEGs). While zonal differences exist within the meniscus tissue (205 DEGs between inner and outer zone meniscus tissue), meniscus resident cells are more similar to each other than to either cartilage or passaged monolayer meniscus cells. Additionally, we identified and validated LUM, PRRX1, and SNTB1 as potential markers for meniscus tissue and ACTA2, TAGLN, SFRP2, and FSTL1 as novel markers for meniscus cell dedifferentiation. Our data contribute significantly to the current characterization of meniscus cells and provide an important foundation for future work in meniscus cell biology, regenerative medicine, and tissue engineering.

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Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity: A Transcriptomic Study

Cited by 4 publications

References 41 publications

Current Knowledge about the Impact of Microgravity on Gene Regulation

Current Knowledge about the Impact of Microgravity on Gene Regulation

Short-term response of primary human meniscus cells to simulated microgravity

Meniscus gene expression profiling of inner and outer zone meniscus tissue compared to cartilage and passaged monolayer meniscus cells

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