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-b 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 meniscusenriched genes were expressed either in the inner or outer meniscus, establishing that regionalization of the meniscus occurs early in development. ß

Hedgehog inhibits β-catenin activity in synovial joint development and osteoarthritis

“…the patellar ligament, leading to local differentiation, as described in tendon-influenced bone eminence formation (40,41). The loss of meniscus formation may result from proliferation of the interzone progeny in the joint space, as identified by Ki67 staining in this study, rather than differentiation, or through dysregulation of multiple genes directing the differentiation of the meniscus (42). However, the specific signals disrupting meniscus formation and selective ectopic cartilage formation observed in this study require further investigation.…”

Meniscus, articular cartilage and nucleus pulposus: a comparative review of cartilage-like tissues in anatomy, development and function

“…Regulation of signaling during development in the meniscus (TGFβ and insulin-like growth factor I) (Pazin et al , 2014), the AC (Wnt9A, GDF5, Erg, Gli3, CD44, type IIA collagen, and type I collagen) (Iwamoto et al , 2007; Koyama et al , 2008; Pacifici et al , 2006), and the NP [Brachyury (T), Shh, Nog, and TGFβ] (Chan et al , 2014) all provide insight toward achieving a tissue-specific cell population. Each of the tissues relies on a variety of disparate signaling pathways to achieve maturation; refinement of these pathways can better progress tissue engineering and regenerative medicine approaches.…”

The Role of Bmp2 in the Maturation and Maintenance of the Murine Knee Joint

“…B ). In contrast, when we looked at genes that define the embryonic meniscus, we found that Dpt , Igf1 , and Igfbp2 were all elevated in menisci from Bmp2 fl/fl ;Gdf5‐Cre knees (Fig. C ).…”

“…(22) RNA isolation and quantitative RT-PCR For meniscal gene expression analysis, medial and lateral menisci isolated from both knees of 2 mice at 2 weeks old of each separate genotype were pooled, homogenized in Trizol, and total RNA isolated as previously described. (23) For articular cartilage gene expression analysis, the cartilage layer of the tibial plateau was carefully separated from the underlying bone of 2week-old mice and pooled from both knees of 2 mice of each separate genotype. The tissue was homogenized in Trizol and total RNA was isolated using the RNeasy Mini Kit (Qiagen, Germantown, MD, USA).…”