Abstract
Synovial joints suffer from arthritis and trauma that may be severely debilitative. Despite robust investigations in the roles of individual genes in synovial joint development and arthritis, little is known about global profiles of genes that regulate stem/progenitor cells of 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 condyle by laser capture microdissection, performed genome-wide profiling, and analyzed molecular signaling pathways relevant to stem/progenitor cell functions. 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 cell homeostasis 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 networks were 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 cells in development, homeostasis, and tissue regeneration.
Highlights
Synovial joint diseases are a substantial burden to society, including arthritis, trauma, and congenital anomalies
BioMed Research International joint is a complex synovial arthrosis with the mandibular condyle serving more than articular cartilage
Mandibular condyles of postnatal 7-day-old mice were frozen-sectioned with articular, mature and hypertrophic zones identified under a dissection microscope (Figure 1(a))
Summary
Synovial joint diseases are a substantial burden to society, including arthritis, trauma, and congenital anomalies. Individual growth and transcriptional factors have been studied primarily to understand joint development and arthritis [1, 2]. Little is known regarding the genes that regulate stem/progenitor cells in homeostasis or pathological conditions of postnatal synovial joints. BioMed Research International joint is a complex synovial arthrosis with the mandibular condyle serving more than articular cartilage. The mandibular condyle is both articular cartilage and an underlying growth plate [3, 4]. Despite the presence of fibrocartilage in the mandibular disk which is functionally equivalent to the knee meniscus, the mandibular condyle shares numerous characteristics of a synovial joint and serves as a pivotal site for bone growth [7, 8]
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