Fibronectin Splicing Variants in Human Intervertebral Disc and Association With Disc Degeneration


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Abstract

Study Design.In this study, normal intervertebral disc (IVD) tissues and degenerative human IVD tissues were compared for presence of fibronectin (FN) mRNA splice variants and for FN fragments (FN-f).Objective.To further understand FN RNA splice forms and protein fragments in disc degeneration.Summary of Background Data.FN splice variants play important roles in regulating cell-matrix and matrix-matrix interactions in skeletogenesis and skeletal function in limbs and other sites. However, presence and possible roles of FN splice variants and fragments in human IVD have not been determined.Methods.Normal infant and adult IVD tissues were obtained from organ donors, and degenerative human IVD tissues were obtained from patients undergoing spinal surgeries. FN splice patterns were assessed by reverse transcriptase polymerase chain reaction. Relative expression levels were semiquantified by densitometry. FN and its fragments were studied by Western blot analysis.Results.Both the EDB+ and EDB splice variants were present in normal and degenerative IVD tissues. The EDB+ to EDB ratio was highest in moderately degenerative tissue. The EDA+ domain was only expressed in infant but not adult tissue. Variable-region (V) splice forms were present in all tissues studied. A splice form with the entire V-region, the 15th type III domain, and 10th type I domain adjacent to the 3′end of V region omitted (referred to as [V+III-15+I-10], also known as [V+C] splice form) was present at higher levels in adult than in infant samples. FN-f were also detected in degenerating tissue, but not in normal IVD tissue samples.Conclusion.The data indicate that higher levels of EDB+ isoform and FN-f are associated with IVD degeneration. This shift in alternative splicing may reflect an attempt of tissue repair and remodeling. Novel information gathered in this study will lead to a better understanding of pathologic processes associated with disc malfunction and degeneration.

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