Session Title: Genetics and Genomics of Rheumatic Diseases
Session Type: Abstract Submissions (ACR)
The role of Wnt signalling in Mesenchymal Stem Cell (MSC) fate is still unclarified. Both, canonical and non-canonical pathways have been implicated in differentiation and proliferation resulting from specific Wnt ligands, receptors, inhibitors and downstream molecules responsible for the signalling and/or the developmental commitment. Although osteogenesis is a well-studied process, molecular details remain unknown. Te aim of the study was to delineate the changes in gene expression of Wnt related occurring during osteogenesis in OA and control patients.
MSCs were obtained from bone marrow aspirates at the time of joint replacement surgery of five OA patients (mean 76 years) and three control subjects without OA signs (mean 80 years). Cells were cultured and expanded under osteogenic stimuli. Confluent cells in passage 6 were collected at days 1, 10 and 21. RNA was purified and retrotranscribed prior quantitative PCR analysis. Simultaneous gene expression of 84 Wnt related genes was analysed using the Human Wnt PCR Array PAHS-043A, from SABiosciences according. The resulting expression raw data was analyzed using the SABiosciences web-based PCR Array Data Analysis tool. ΔΔCt values relative to the RPL13A housekeeping gene were used to calculate the expression changes. Two-fold changes with p<0.05 were considered significative.
MSCs from OA patients undergoing osteogenesis progressively increases the number of downregulated genes related to the Wnt signaling. While at basal conditions only two genes were downregulated, at days 10 and 21, twelve and sixteen genes were downregulated respectively. Among downregulated genes, some encode for essential proteins participating both in canonical and non-canonical Wnt pathway and including several ligands, co-rreceptors, inhibitors, kinases and transcription factors.
Our data demosnstrate a clear alteration during osteogenesis of MSCs biology from OA patients. We hypothesized that a possible cause of OA may lie in these intrinsic alterations of MSCs preventing proper differentiation into fully functional adult tissues.
J. R. Lamas,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dynamic-gene-expression-of-wnt-signaling-pathway-during-osteogenic-stimulation-in-vitro-of-osteoarthritis-mesenchymal-stem-cells/