Ubiquitin-dependent proteolysis of CXCL7 leads to posterior longitudinal ligament ossification

PloS One
Michiyo TsuruKensei Nagata

Abstract

Ossification of the posterior longitudinal ligament (OPLL), a spinal ligament, reduces the range of motion in limbs. No treatment is currently available for OPLL, which is why therapies are urgently needed. OPLL occurs in obesity, is more common in men, and has an onset after 40 years of age. The mechanisms underlying OPLL remain unclear. In this study, we performed a serum proteomic analysis in both OPLL patients and healthy subjects to identify factors potentially involved in the development of OPLL, and found reduced levels of a protein that might underlie the pathology of OPLL. We isolated the protein, determined its amino acid sequence, and identified it as chemokine (C-X-C motif) ligand 7 (CXCL7). Based on these proteomics findings, we generated a CXCL7 knockout mouse model to study the molecular mechanisms underlying OPLL. CXCL7-null mice presented with a phenotype of OPLL, showing motor impairment, heterotopic ossification in the posterior ligament tissue, and osteoporosis in vertebrate tissue. To identify the mechanisms of CXCL7 deficiency in OPLL, we searched for single nucleotide polymorphisms and altered DNA exons, but no abnormalities were found. Although miR-340 levels were found to be high in an miRNA array, they...Continue Reading

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Datasets Mentioned

BETA
GES57590
GES57592
GSE57590
GSE57592

Methods Mentioned

BETA
chip
protein chip
chips
Genotyping
Assay
gene knockout
gene trap
fluorescence microscopy
electrophoresis
density-gradient centrifugation

Software Mentioned

DAVID
SAS
Freezer
PDQuest
Mascot

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