RGD Reference Report - Structural, compositional, and biomechanical alterations of the lumbar spine in rats with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome). - Rat Genome Database

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Structural, compositional, and biomechanical alterations of the lumbar spine in rats with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome).

Authors: Lai, A  Simonaro, CM  Schuchman, EH  Ge, Y  Laudier, DM  Iatridis, JC 
Citation: Lai A, etal., J Orthop Res. 2013 Apr;31(4):621-31. doi: 10.1002/jor.22281. Epub 2012 Nov 28.
RGD ID: 10043113
Pubmed: (View Article at PubMed) PMID:23192728
DOI: Full-text: DOI:10.1002/jor.22281

Mucopolysaccharidosis (MPS) VI is an inherited lysosomal storage disorder resulting from deficiency of N-acetylgalactosamine-4-sulfatase activity and subsequent accumulation of incompletely degraded dermatan sulfate (DS) containing glycosaminoglycans (GAGs). Painful spinal deformities are commonly found in MPS VI patients. We characterized lumbar spine structure, composition, and biomechanics in a naturally occurring rat MPS VI model and evaluated the role of MMP-13, ADAMTS-5 and TNF-alpha in modulating the observed changes. MPS VI rats had discs with large vacuolated cells and sizable nuclear defects. MPS spine segments also had structural and functional changes suggestive of spinal instability, including decreased nuclear pressurization, increased joint laxity and increased disc height index. These functional changes were at least partly associated with elevated ADAMTS-5, MMP-13, and TNF-alpha. Vertebral and endplate biomechanics were also affected by MPS VI with decreased failure load and stiffness. The discal and vertebral dysfunctions observed in MPS VI rats are likely to be associated with pathological spinal conditions, similar to those that afflict MPS patients. Our findings also suggest more broadly that abnormal accumulation of GAGs and the associated chronic pro-inflammatory and catabolic cascade may also be a source of spinal dysfunction.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Adamts5  (ADAM metallopeptidase with thrombospondin type 1 motif, 5)

Genes (Mus musculus)
Adamts5  (a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5 (aggrecanase-2))

Genes (Homo sapiens)
ADAMTS5  (ADAM metallopeptidase with thrombospondin type 1 motif 5)


Additional Information