Evaluation of 12 Novel Molecular Markers for Degenerated Nucleus Pulposus in a Chinese Population.

Abstract

STUDY DESIGN:

A transcriptional expression assessment of human samples.

OBJECTIVE:

To evaluate 12 new candidate nucleus pulposus (NP) markers in degenerative disc disease in a Chinese population.

SUMMARY OF BACKGROUND DATA:

Disc degeneration is a major contributor of low back pain. However, no specific and reliable markers of degeneration of NP are available.

METHODS:

Specimens of NP were collected from 81 patients and grouped into the degenerated disc group (undergoing discectomy and fusion with significant signs of disc degeneration) and the trauma control group (undergoing anterior vertebral body and disc excision and fusion without signs of disc degeneration). Lumbar spine magnetic resonance imaging, hematoxylin-eosin staining, and safranin O staining of sections of NP tissues were conducted to evaluate the severity of the disc degeneration in all samples. Quantitative reverse transcription polymerase chain reaction was performed to investigate the levels of mRNA expression of these genes, as well as those of aggrecan, type II collagen, and SRY-box 9 (SOX-9). Degenerated samples were also divided into groups according to Pfirrmann grading system to elucidate the association of severity of degeneration and gene transcriptional levels. We also tested the relationship between mRNA levels of these genes and clinical characteristics such as hypertension and diabetes mellitus.

RESULTS:

We demonstrated that 11 of the 12 candidates showed significant differential expression in degenerated discs. Changes in the expression of these 11 genes were determined to be risk factors in degenerative disc diseases. The expression of neurochondrin (NCDN), keratin 8 (KRT8), and matrix Gla protein (MGP) even showed significant changes among subgroups of patients with degenerative disc disease stratified according to the Pfirrmann grading system. The expression of keratin 18 (KRT18), cadherin 2 (CDH2), synaptosomal-associated protein 25 (SNAP25), KRT8, and NCDN was significantly decreased in patients with hypertension. In contrast, the expression of MGP and cartilage oligomeric matrix protein was significantly upregulated in patients with diabetes mellitus.

CONCLUSION:

Overall, we demonstrated the clinical utility of 11 novel NP markers for degenerative disc disease. Among them, the expression of NCDN, KRT8, and MGP may indicate the severity of disc degeneration.

LEVEL OF EVIDENCE:

N/A.

• Authors: Shuai Chen, Zhi-Jun Hu, Zhi-Jie Zhou, Xian-Feng Lin, Feng-Dong Zhao, Jian-Jun Ma, Jian-Feng Zhang, Ji-Ying Wang, An Qin, Shun-Wu Fan
• Journal: Spine (Spine (Phila Pa 1976)) Vol. 40 Issue 16 Pg. 1252-60 (Aug 15 2015) ISSN: 1528-1159 [Electronic] United States
• PMID: 25893345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BASP1 protein, human
• Biomarkers
• Cadherins
• Calcium-Binding Proteins
• Cartilage Oligomeric Matrix Protein
• Extracellular Matrix Proteins
• Keratin-18
• Keratin-19
• Keratin-8
• Membrane Proteins
• Nerve Tissue Proteins
• RNA, Messenger
• Receptors, Virus
• Repressor Proteins
• Synaptosomal-Associated Protein 25
• matrix Gla protein
• neurochondrin
• poliovirus receptor
• Neuropilin-1

Topics

• Adult
• Aged
• Aged, 80 and over
• Asian People (genetics)
• Biomarkers
• Cadherins (genetics)
• Calcium-Binding Proteins (genetics)
• Cartilage Oligomeric Matrix Protein (genetics)
• Case-Control Studies
• China
• Diabetes Mellitus (genetics)
• Extracellular Matrix Proteins (genetics)
• Female
• Humans
• Hypertension (genetics)
• Intervertebral Disc Degeneration (genetics, pathology)
• Keratin-18 (genetics)
• Keratin-19 (genetics)
• Keratin-8 (genetics)
• Lumbar Vertebrae
• Magnetic Resonance Imaging
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Nerve Tissue Proteins (genetics)
• Neuropilin-1 (genetics)
• RNA, Messenger (metabolism)
• Receptors, Virus (genetics)
• Repressor Proteins (genetics)
• Severity of Illness Index
• Synaptosomal-Associated Protein 25 (genetics)
• Transcription, Genetic