Dataset Information

Simulated microgravity inspired osteoarthritis model reveals CD36 as a sex dimorphic drug target

ABSTRACT: Osteoarthritis (OA) is a prevalent and debilitating disease that predominantly affects load-bearing joints (1). Knee osteoarthritis (KOA) is characterized by the progressive degradation of nearly all structures within the knee joint, leading to pain, stiffness, and reduced joint mobility (2-4). The meniscus, a critical fibrocartilaginous structure, plays an essential role in joint stability, load distribution, and shock absorption (5). Meniscus degeneration is one of the earliest pathological changes observed in the onset of knee OA (6, 7), highlighting the importance of understanding the molecular mechanisms contributing to its deterioration. The meniscus operates under constantly loaded biomechanical environments, making appropriate mechanical stress critical for maintaining a healthy phenotype. Conditions of reduced mechanical stress on Earth or microgravity induced by parabolic flight or spaceflight have been demonstrated to induce the onset of KOA phenotype and initiate tissue degeneration in both animal models (28-31) and human subjects (32-35). Simulated microgravity (SMG) provides a unique platform to study the mechanical unloading environment of microgravity on Earth, making it a relevant model system for investigating KOA mechanisms. Previous studies on both short-term and long-term SMG have shown that SMG can initiate the development of KOA phenotypes and promote tissue degeneration, with observed sex differences (36-40).

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Meniscus

SUBMITTER: Daniel Young

LAB HEAD: Antoine Dufour

PROVIDER: PXD064341 | Pride | 2026-04-27

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	2025-1-24_Hilda_Meniscus_Calcification.zip	Other
	S17674_28_Meniscus_Calcification_1_250116.raw	Raw
	S17675_29_Meniscus_Calcification_2_250116.raw	Raw
	S17676_30_Meniscus_Calcification_3_250116.raw	Raw
	S17677_31_Meniscus_Calcification_4_250116.raw	Raw

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Publications

Simulated microgravity models sex differences in knee osteoarthritis through a CD36-regulated mechano-metabolic circuit.

Ma Zhiyao Z Lin Haiming H Young Daniel D Ansari Aahil A Kunze Melanie M Mulet-Sierra Aillette A Febbraio Maria M Graf Daniel D Dufour Antoine A Adesida Adetola B AB

Cell communication and signaling : CCS 20260314 1

PMID: 41832555

Similar Datasets

Project description:Leveraging the unique conditions of space microgravity, our research offers groundbreaking insights into osteoarthritis (OA), a degenerative joint disease impacting over three million Canadians and predominantly affecting load-bearing joints such as the knee. With knee OA (KOA) known for its higher incidence and severity among females—a phenomenon not fully explained by existing risk factors—the application of simulated microgravity (SMG) presents a novel approach to understanding the disease's progression and the biological sex differences in response to it. By employing rotating wall vessel (RWV) technology to simulate spaceflight conditions on Earth, our studies focus on the biomechanical unloading experienced in microgravity, which has been observed to induce OA-like changes in articular tissues. This innovative research strategy allows us to explore the potential mechanisms of OA development and progression in a controlled environment, mimicking the microgravity of space to provide new perspectives on the disease's molecular underpinnings. Initial results from our investigations reveal that SMG significantly alters the molecular expression profiles in engineered meniscus constructs derived from non-KOA patients, notably influencing genes related to chondrocyte hypertrophy and OA progression while downregulating protective genes. Further analysis has illuminated sex-specific molecular responses to SMG, demonstrating pronounced differences between male and female specimens. This highlights the importance of considering biological sex in OA research, as it significantly influences disease development and response to microgravity conditions. Extended RNA sequencing under SMG conditions has identified distinct molecular signatures for different sex-based groups, pointing towards an OA-like transcriptome profile in females particularly responsive to SMG. One of the most significant findings from our microgravity studies is the modulation of CD36, a transmembrane protein implicated in lipid metabolism and OA pathogenesis. Its altered expression under SMG conditions and known upregulation in KOA patients underscore the potential mechanisms by which microgravity-induced cellular responses can mimic and inform us about OA development, particularly in terms of sex-specific disparities.

Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.