Analysis of meniscal degeneration and meniscal gene expression

Abstract

BackgroundMenisci play a vital role in load transmission, shock absorption and joint stability. 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, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells.MethodsStudies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR.ResultsThe grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many of the 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 significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and prostaglandin E synthase (PTGES), were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific.ConclusionOur 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.

Molecular Analysis of Age and Sex-Related Gene Expression in Meniscal Tears with and without a Concomitant Anterior Cruciate Ligament Tear

“…The expression pattern of multiple proinflammatory cytokines, chemokines, matrix-degrading enzymes, matrix genes, and transcription factors is an important consideration in the molecular characterization of osteoarthritis 2 . Among patients with an isolated meniscal tear, those younger than forty years had elevated levels of several of the osteoarthritis-related genes compared with patients older than forty years.…”

“…Its complex pathogenesis remains poorly understood but appears multifactorial, with emerging evidence that osteoarthritis is not merely an articular cartilage disease, but a disease of the whole joint 1,2 , involving cartilage 3 , bone 4 , synovium 5 , and meniscus 6,7 . The meniscus functions as a load-bearing 8 and shock-absorbing 9 part of the tibiofemoral joint.…”

Abnormal Mechanical Loading Induces Cartilage Degeneration by Accelerating Meniscus Hypertrophy and Mineralization After ACL Injuries In Vivo

“…The severity of cartilage damage was determined by the Osteoarthritis Research Society International (OARSI) histological score after the slides were stained using safranin O/Fast Green, 22 and the severity of meniscus damage was graded grossly. 36 Three independent blinded observers scored each section. The association between the area and intensity of meniscus calcification and the severity of cartilage damage was established using regression analysis.…”

Bone and Cartilage from Stem Cells: Growth Optimalization and Stabilization of Cell Phenotypes

“…Hence, it is necessary to identify a transcriptome, which is reflecting the "true" osteoblast and chondrocyte phenotypes pertaining to the function and localization of such cells in the skeleton. Many excellent articles have addressed this task over the past 10 years, of which only some are mentioned here (Kulterer, Friedl et al 2007;Grundberg, Brandstrom et al 2008;Duggal, Fronsdal et al 2009;Morsczeck, Schmalz et al 2009;Sundelacruz and Kaplan 2009;Bernstein, Sticht et al 2010;Granchi, Ochoa et al 2010;Piek, Sleumer et al 2010;Sun, Mauerhan et al 2010;van der Zande, Walboomers et al 2010;Herlofsen, Kuchler et al 2011). Two transcriptomes featuring putative gene markers of osteoblasts and chondrocytes (two each), respectively, will be described in detail.…”