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L. Shelton, J.S. Rada; In vitro Characterization of Bone Morphogenetic Proteins and Sclerostin in Scleral Extracellular Matrix Remodeling . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1804.
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Myopia (Nearsightedness) is commonly the result of excessive elongation of the vitreous chamber that is facilitated by extracellular matrix remodeling in the posterior sclera. Based on preliminary data and previous studies in cartilage and ligament fibroblasts, we hypothesize that bone morphogenetic proteins (BMPs) and one of their associated inhibitors (sclerostin, SOST) may play a role in the regulation of ocular growth by modulating proteoglycan synthesis rates and/or matrix metalloproteinase (MMP–2) activities in the sclera.
Human scleral fibroblasts were treated in vitro with BMP–6, BMP–7 (10 – 300 ng/ml) or sclerostin (0.1 – 2.5 µg/ml). Proteoglycan synthesis and pro– and active MMP–2 levels were measured in culture medium of treated and control scleral fibroblasts using 35[SO4] incorporation into glycosaminoglycans and gelatin zymography, respectively, and values were normalized to total protein and/or DNA concentrations for each culture well.
Treatment of HSFs with BMP–6 or BMP–7 (10 ng/ml) resulted in a significant increase (p< 0.05, two–tailed t–test) in proteoglycan synthesis, whereas treatment with sclerostin alone had no significant effects. BMP–6, –7 and sclerostin treated cells revealed no significant differences in total protein concentration. Treatment of HSFs with BMP–6 or –7 (100 ng/ml) resulted in significant decreases in the synthesis of the MMP–2 pro–enzyme (–45.7%, –46.5%, respectively, p<0.05, ANOVA) while treatment of scleral fibroblasts with sclerostin alone had no significant effects.
The results of this study suggest that BMP–6 and –7 may facilitate scleral extracellular matrix accumulation and decrease matix turnover through increases in proteoglycan synthesis and decreases in MMP–2 pro–enzyme levels. Information from future studies may be applied towards characterizing the molecular events associated with the development of myopia in humans.
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