RESUMEN
Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor ß1 (TGFß1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFß1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible.
Asunto(s)
Anillo Fibroso/metabolismo , Matriz Extracelular/metabolismo , Regulación de la Expresión Génica/genética , Degeneración del Disco Intervertebral/metabolismo , Desplazamiento del Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Anillo Fibroso/patología , Proteína Morfogenética Ósea 2/farmacología , Células Cultivadas , Matriz Extracelular/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral/genética , Desplazamiento del Disco Intervertebral/patología , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Regeneración/efectos de los fármacos , Regeneración/genética , Factor de Crecimiento Transformador beta1/farmacología , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: The combination of a bony injury to the shoulder girdle and damage to the brachial plexus and the subclavian vessels is a rare finding. The cases of this combined injury pattern described in the literature are most notably reported in multiply-injured patients after high velocity trauma. FINDINGS: Three cases were admitted to our hospital after motorcycle accidents resulting in a combination of severe bony injuries to the shoulder girdle, to the subclavian artery and a lesion to the brachial plexus. Based on these three clinical cases the patterns of injury, as well as primary and secondary treatment approaches are presented. CONCLUSION: The early detection of these injuries can be difficult in given acute, life threatening injuries addressed first in these multiply injured patients. A high level of suspicion, in conjunction with standardized ATLS based institutional protocols for secondary and tertiary survey, should increase the likelihood of a timely detection and early management of these rare but potentially devastating injuries.