Gene signature of the embryonic meniscus

Abstract

The meniscus is a fibrocartilagenous disc in the knee that protects the joint from damage. Meniscal injuries are common, however repair efforts are largely unsuccessful and are not able to prevent the degenerative changes that result in development of osteoarthritis. Tissue regeneration in adults often recapitulates events of embryonic development, suggesting the regulatory pathways controlling morphogenesis are candidate repair signals. Here we use laser capture microdissection to collect mouse embryonic day 16 (E16) meniscus, articular cartilage, and cruciate ligaments. RNA isolated from these tissues was then used to perform genome-wide microarray analysis. We found 38 genes were differentially expressed between E16 meniscus and articular cartilage and 43 genes were differentially expressed between E16 meniscus and cruciate ligaments. Included in our data set were extracellular matrix proteins, transcription factors, and growth factors, including TGF-β modulators (Lox, Dpt) and IGF-1 pathway members (Igf-1, Igfbp2, Igfbp3, Igfbp5). Ingenuity Pathway Analysis revealed that IGF-1 signaling was enriched in the meniscus compared to the other joint structures, while qPCR showed that Igf-1, Igfbp2, and Igfbp3 expression declined with age. We also found that several meniscus-enriched genes were expressed either in the inner or outer meniscus, establishing that regionalization of the meniscus occurs early in development.