OR24-3 Upregulation of type I collagen genes in osteogenesis imperfecta patients

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR24-New Mechanisms in Bone Biology: From Cells to Genetics, & Mice to Men
Sunday, June 16, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:45 AM
Room 121 (Moscone Center)
Lilia Freire Rodrigues D'Souza-Li*1, Marcus Vinicius Pedroni2, Marcelo Ananias Teocchi3, Javier Adur4, Ana Erika Dias Ferreira1, Carlos L. Cesar4 and Carlos E. Steiner1
1Faculty of Medical Science, University of Campinas, UNICAMP, Campinas, Brazil, 2Faculty of Medical Science, University of Campinas, Campinas, 3Faculty of Medical Science, University of Campinas, Campinas, Brazil, 4“Gleb Wataghin” Institute of Physics, University of Campinas UNICAMP, Campinas, Brazil
Introduction: Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility. The objective of this study was to perform functional analyses of type I collagen genes in OI patients. Methods: We studied nine patients presenting as variable phenotypes of types I, III and IV OI with heterozygous missense mutations in COL1A1 or COL1A2. Utilizing a combination of two-photon excitation fluorescence (TPEF) and second-harmonic generation (SHG) microscopes images, quantification of collagen density, intensity and texture analysis were performed. To analyze the depth-dependent decay (DDD) of the SHG signal we took a series of SHG images at intervals of 1 μm up to a final depth of 40 μm; this calculation was performed using Plot Z-axis Profile commands from Image/Stack and quantified using ImageJ software. Results: We found that both the wild type and the mutant transcripts COL1A1 and COL1A2 genes were significantly upregulated among OI patients (Mann–Whitney U test, COL1A1 P = 0.002;COL1A2 P = 0.008). A decrease in SHG signal intensity with increase depth was observed in OI tissues while normal skin showed similar collagen intensity in almost all volume examined. When plotting the depth-dependent decay (DDD) of the SHG signal we found that the OI skin dermis had a significant lower DDD, demonstrating that collagen in OI patient was less densely packed. When we checked the amount and distribution of collagen, patients with OI presented a slight increase in collagen content (8.49±0.64 mild and 6.37±0.85 severe) compared to normal skin (5.07±1.03), with mild OI presented statistically significant difference (p<0.05). Conclusion: Patients with OI presented hyperexpression of type I collagen genes with slight increase in collagen content. However, their collagen is not evenly distributed in skin. This study contributes to the understanding of OI expression, localization, and organization of mutant and normal type I collagen polypeptide chains.

Nothing to Disclose: LFRD, MVP, MAT, JA, AEDF, CLC, CES

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