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RNA sequencing of human meniscal fibrochondrocytes treated with 17beta-estradiol

ABSTRACT: Meniscal tears are the most prevalent intra-articular knee injury and pose significant risk in the development of knee osteoarthritis, a progressive disease that affects around 250 million people worldwide. Meniscus tissue, especially the avascular inner third, heals poorly and the only treatment option is surgery. Epidemiological data and the vital role of estrogen in tissue repair and homeostasis indicate that estrogen could be fundamental for knee joint health and could be useful for tissue regeneration. However, the specific cell response to estrogen and the differences in response of cells from different donors is unknown. In this study, RNA sequencing was used to characterize the mRNA transcriptome of human meniscal cells from male (47-year-old) and female (16-, 17-, and 47-year-old) donors treated with 17beta-estradiol. The goal is to provide data valuable to the design and implementation of estrogen replacement therapies for meniscal health and osteoarthritis reduction.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199087 | GEO | 2022/09/16

REPOSITORIES: GEO

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Project description:Menisci play a vital role in load transmission, shock absorption and joint stability. The current dogma is that the menisci simply protects the cartilage and play no role in osteoarthritis (OA) unless they are injured. However, there is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, 2) to examine gene expression in OA meniscal cells compared to normal control meniscal cells, and 3) to test the hypothesis that OA meniscal cells are different from normal meniscal cells. The grades of meniscal degeneration correlated in a positive fashion with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), integrin, beta 2 (ITGB2), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ankylosis, progressive homolog (ANKH) and fibroblast growth factor 7 (FGF7), were expressed at higher levels compared to normal control meniscal cells. In addition, many genes that were previously implicated in OA were also expressed at higher levels in OA meniscal cells, including ADAM metallopeptidase with thrombospondin type 1 motif, 5 (ADAMTS5). Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA. Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients (OA specimens) and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from the meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal control meniscal cells was examined using Affymetrix microarray and real time RT-PCR.

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RNA sequencing of human meniscal fibrochondrocytes treated with 17beta-estradiol

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