As one of the common birth defects worldwide, nonsyndromic microtia is a complex disease that results from interactions between environmental and genetic factors. However, the underlying causes of nonsyndromic microtia are currently not well understood. The present study determined transcriptomic and proteomic profiles of auricular cartilage tissues in 10 patients with third-degree nonsyndromic microtia and five control subjects by RNA microarray and tandem mass tag-based quantitative proteomics technology. Relative mRNA and protein abundances were compared and evaluated for their function and putative involvement in nonsyndromic microtia. A total of 3971 differentially expressed genes and 256 differentially expressed proteins were identified. Bioinformatics analysis demonstrated that some of these genes and proteins showed potential associations with nonsyndromic microtia. Thirteen proteins with the same trend at the mRNA level obtained by the integrated analysis were validated by parallel reaction monitoring analysis. Several key genes, namely, LAMB 2 , COMP , APOA 2, APOC 2, APOC 3, and A 2 M , were found to be dysregulated, which could contribute to nonsyndromic microtia. The present study is the first report on the transcriptomic and proteomic integrated analysis of nonsyndromic microtia using the same auricular cartilage sample. Additional studies are required to clarify the roles of potential key genes in nonsyndromic microtia.
Objectives: Ear molding is an emerging technique that can correct auricular deformities. Treatment initiation time is the most important prognostic determinant of ear molding. Here, we aimed to examine why auricular cartilage plasticity appeared to diminish with age. Thus, we characterized age-related changes in the biomechanical, biochemical, and morphological properties of auricular cartilage.Methods: New Zealand rabbits were used as the experimental animal. We examined immature [postnatal 0 day (P0), 5 days (P5), 15 days (P15)], young [2 months (2M)], and mature [6 months (6M)] rabbits. Rabbits' ears were splinted and folded using adhesive fixation strips. Folding duration ranged from 1 day to 5 days to 10 days. Photographs were taken to calculate the retained fold angle. Cartilage morphology and extracellular matrix (ECM) content were examined histologically (using hematoxylin-eosin, Safranin O, elastic Van Gieson, and Masson's trichrome). Water content, DNA content, and cell density were also analyzed. Biomechanical properties were measured using a Nano indenter.Results: Immature ears had smaller angles after strip removal, and the angled deformation lasted a longer time. Cartilage matrix compositions, including glycosaminoglycan (GAG), elastin fiber, and collagen, increased over development. The water content, DNA content, and cell density decreased with age. Young's modulus was significantly higher in mature cartilage.Conclusions: Here, we successfully established an animal model of ear molding and demonstrated that immature cartilage was associated with better plasticity. We also found that the cartilage's biomechanical property increased with the accumulation of ECM. The biomechanical change could underlie age-related shape plasticity.
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