Profiling of Stem/Progenitor Cell Regulatory Genes of the Synovial Joint by Genome-Wide RNA-Seq Analysis

Synovial jointssuffer from arthritis and trauma that may be severely debilitative. Despite robust investigations in the roles of individual genes in synovial jointdevelopment and arthritis, little is known about global profiles of genes that regulate stem/ progenitor cellsof a synovial joint. The temporomandibular joint is a poorly understood synovial arthrosis with few clinical treatment options. Here, we isolated the articular and mature zones of the mandibular condyleby laser capture microdissection, performed genome-wide profiling, and analyzed molecular signaling pathways relevant to stem/ progenitor cellfunctions. A total of 804 genes were differentially expressed between the articular and mature zones. Pathway analyses revealed 29 enriched signaling pathways, including the PI3K-Akt, Wnt, and Toll-like receptor signaling pathways that may regulate stem/ progenitor cellhomeostasis and differentiation into the chondrocyte lineage. Upstream regulator analyses further predicted potential upstream key regulators such as Xbp1, Nupr1, and Hif1a, and associated underlying mechanism networkswere described. Among the multiple candidates of growth and transcriptional factors that may regulate stem/ progenitor cells, we immunolocalized Sox9, Ihh, Frzb, Dkk1, Lgr5, and TGFβ3 in the articular and mature zones. These findings provide a comprehensive genetic mapping of growth and transcriptional genes in the articular and mature zones of a synovial joint condyle. Differentially expressed genes may play crucial roles in the regulation of stem/ progenitor cellsin development, homeostasis, and tissue regeneration.