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Molecular basis of degenerative spinal disorders from a proteomic perspective (Review).

ABSTRACT: Intervertebral disc degeneration (IDD) and ligamentum flavum hypertrophy (LFH) are major causes of degenerative spinal disorders. Comparative and proteomic analysis was used to identify differentially expressed proteins (DEPs) in IDD and LFH discs compared with normal discs. Subsequent gene ontology term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEPs in human IDD discs or LFH samples were performed to identify the biological processes and signaling pathways involved in IDD and LFH. The PI3K?AKT signaling pathway, advanced glycation endproducts?receptor for advanced glycation endproducts signaling pathway, p53 signaling pathway, and transforming growth factor?b signaling pathway were activated in disc degeneration. This review summarizes the recently identified DEPs, including prolargin, fibronectin 1, cartilage intermediate layer protein, cartilage oligomeric matrix protein, and collagen types I, II and IV, and their pathophysiological roles in degenerative spinal disorders, and may provide a deeper understanding of the pathological processes of human generative spinal disorders. The present review aimed to summarize significantly changed proteins in degenerative spinal disorders and provide a deeper understanding to prevent these diseases.

SUBMITTER: Liu C

PROVIDER: S-EPMC6896343 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Molecular basis of degenerative spinal disorders from a proteomic perspective (Review).

Liu Chang C Yang Minghui M Liu Libangxi L Zhang Yang Y Zhu Qi Q Huang Cong C Wang Hongwei H Zhang Yaqing Y Li Haiyin H Li Changqing C Huang Bo B Feng Chencheng C Zhou Yue Y

Molecular medicine reports 20191112 1

Intervertebral disc degeneration (IDD) and ligamentum flavum hypertrophy (LFH) are major causes of degenerative spinal disorders. Comparative and proteomic analysis was used to identify differentially expressed proteins (DEPs) in IDD and LFH discs compared with normal discs. Subsequent gene ontology term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEPs in human IDD discs or LFH samples were performed to identify the biological processes and ...[more]

PMID: 31746390

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Project description:Lysosomal storage disorders (LSDs) are a large group of more than 50 different inherited metabolic diseases which, in the great majority of cases, result from the defective function of specific lysosomal enzymes and, in few cases, of non-enzymatic lysosomal proteins or non-lysosomal proteins involved in lysosomal biogenesis. The progressive lysosomal accumulation of undegraded metabolites results in generalised cell and tissue dysfunction, and, therefore, multi-systemic pathology. Storage may begin during early embryonic development, and the clinical presentation for LSDs can vary from an early and severe phenotype to late-onset mild disease. The diagnosis of most LSDs--after accurate clinical/paraclinical evaluation, including the analysis of some urinary metabolites--is based mainly on the detection of a specific enzymatic deficiency. In these cases, molecular genetic testing (MGT) can refine the enzymatic diagnosis. Once the genotype of an individual LSD patient has been ascertained, genetic counselling should include prediction of the possible phenotype and the identification of carriers in the family at risk. MGT is essential for the identification of genetic disorders resulting from non-enzymatic lysosomal protein defects and is complementary to biochemical genetic testing (BGT) in complex situations, such as in cases of enzymatic pseudodeficiencies. Prenatal diagnosis is performed on the most appropriate samples, which include fresh or cultured chorionic villus sampling or cultured amniotic fluid. The choice of the test--enzymatic and/or molecular--is based on the characteristics of the defect to be investigated. For prenatal MGT, the genotype of the family index case must be known. The availability of both tests, enzymatic and molecular, enormously increases the reliability of the entire prenatal diagnostic procedure. To conclude, BGT and MGT are mostly complementary for post- and prenatal diagnosis of LSDs. Whenever genotype/phenotype correlations are available, they can be helpful in prognosis and in making decisions about therapy.

Project description:AimsPatients may present with concurrent symptomatic osteoarthritis (OA) of the hip and degenerative disorders of the lumbar spine, with surgical treatment being indicated for both. Whether arthroplasty of the hip or spinal surgery should be performed first remains uncertain.Materials and methodsClinical scenarios were devised for a survey asking the preferred order of surgery and the rationale for this decision for five fictional patients with both OA of the hip and degenerative lumbar disorders. These were symptomatic OA of the hip and: 1) lumbar spinal stenosis with neurological claudication; 2) lumbar degenerative spondylolisthesis with leg pain; 3) lumbar disc herniation with leg weakness; 4) lumbar scoliosis with back pain; and 5) thoracolumbar disc herniation with myelopathy. This survey was sent to 110 members of The Hip Society and 101 members of the Scoliosis Research Society. The choices of the surgeons were compared among scenarios and between surgical specialties using the chi-squared test. The free-text comments were analyzed using text-mining.ResultsResponses were received from 51 hip surgeons (46%) and 37 spine surgeons (37%). The percentages of hip surgeons recommending 'hip first' differed significantly among scenarios: 59% for scenario 1; 73% for scenario 2; 47% for scenario 3; 47% for scenario 4; and 10% for scenario 5 (p < 0.001). The percentages of spine surgeons recommending 'hip first' were 49% for scenario 1; 70% for scenario 2; 19% for scenario 3; 78% for scenario 4; and 0% for scenario 5. There were significant differences between the groups for scenarios 3 (more hip surgeons recommended 'hip first'; p = 0.012) and 4 (more hip surgeons recommended 'spine first'; p = 0.006).ConclusionIn patients with coexistent OA of the hip and degenerative disorders of the spine, the question of 'hip or spinal surgery first' elicits relatively consistent answers in some clinical scenarios, but remains controversial in others, even for experienced surgeons. The nature of neurological symptoms can influence surgeons' decision-making. Cite this article: Bone Joint J 2019;101-B(6 Supple B):37-44.

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Molecular basis of degenerative spinal disorders from a proteomic perspective (Review).

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Molecular basis of degenerative spinal disorders from a proteomic perspective (Review).

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