Immuohistochemical score of matrix metalloproteinase-1 may indicate the severity of symptomatic cervical and lumbar disc degeneration.

BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration is related to numerous risk factors, including obesity. Leptin, one of the commonly measured adipokines, is proven to play an important role in the pathogenesis of IVD degeneration. In the context of IVD degeneration, matrix metalloproteinase-1 (MMP-1), which is upregulated and activated by leptin, is the most abundant catabolic enzyme. It remains unclear which of the factors mentioned above is most strongly associated with IVD degeneration. PURPOSE: To investigate the influence of MMP-1 in IVD degeneration, we determined the strength of different predictors, including age, sex, magnetic resonance imaging (MRI), Modic changes (MCs), body mass index (BMI), leptin, and MMP-1. This was achieved by assessing the correlation among these factors and histologic degeneration score (HDS). STUDY DESIGN: This study included 89 patients undergoing cervical discectomy for disc herniation, 93 who underwent lumbar discectomy, and 90 control subjects. Herniated disc tissue and plasma were used after the study was approved by the Human Ethics Review Committee at the authors' institution. METHODS: Hematoxylin and eosin (H&E), Alcian blue-PAS and immunohistochemical (IHC) staining were performed to measure the expression levels of leptin and MMP-1. Circulating plasma levels of leptin and MMP-1 were measured using an enzyme-linked immunosorbent assay. To assess the correlation with HDS, measurements of age, sex, BMI, MRI scale, MCs scale, leptin/MMP-1 plasma concentration, and leptin/MMP-1 IHC expression were analyzed. RESULTS: Patients with cervical or lumbar discectomy had significantly higher BMI than controls. Significantly more men than women were involved in the lumbar patients as compared with the cervical patients and the control subjects. After adjustment for age and sex, plasma leptin and leptin IHC score correlated significantly with BMI in patients with cervical or lumbar discectomy. Age, sex, MRI scale, MCs scale, and leptin/MMP-1 plasma concentration were not positively correlated with HDS. HDS was significantly associated with BMI, leptin IHC score, and MMP-1 IHC score. After a stepwise-multiple linear regression analysis to evaluate the strength of the correlations between HDS and various factors, only the MMP-1 IHC score demonstrated an independent association with HDS in patients with degeneration of the cervical or lumbar disc. CONCLUSIONS: MMP-1 IHC score is an independent predictor of the severity of cervical or lumbar IVD degeneration. CLINICAL SIGNIFICANCE: MMP-1 IHC score may be used as an indicator of IVD degeneration.

Validation of the intervertebral disc histological degeneration score in cervical intervertebral discs and their end plates.

BACKGROUND CONTEXT: Vertebral joints consist of intervertebral discs (IVDs) and cartilaginous end plates (EP) that lie superiorly and inferiorly to the IVDs and separate them from the adjacent vertebral bodies. With aging, both IVDs and EPs undergo degeneration. The Histologic Degeneration Score (HDS) is a grading system that microscopically evaluates the degree of degeneration in lumbar discs and predicts it with high accuracy basing on several histological markers of IVD and EP. There is currently a lack of validated histologic grading schemes for cervical spine degeneration. PURPOSE: The aim of our study was to describe the changes in cervical IVDs and EPs with degeneration and to test the validity of the HDS in the cervical spine. STUDY DESIGN: A histological study on degenerative changes in cervical IVDs and EPs was conducted. METHODS: Thirty human cadavers were dissected to obtain 60 cervical IVDs from the lower half of C4 to the level of the upper half of C6. The IVDs were carefully excised along with EPs and then sectioned to obtain midsagittal samples for macroscopic examination according to a five-grade classification system. The samples were further dissected, fixed, and stained for histological examination according to HDS. RESULTS: Thirty C4-C5 IVDs and thirty C5-C6 IVDs were macroscopically examined for degeneration. The averaged Thompson's grade was found to be 2.9±1.3. The mean HDS for IVDs was 13.1±5.8 and for EP was 10.2±5.2. The interrater reliability estimates indicated excellent reliability (κ values>0.81, percentage agreement 86.1%-96.1%). Spearman's rank correlation coefficients for IVD and EP scores showed good consistency in predicting macroscopic degeneration. No significant differences were found between the values for cervical IVDs and EPs in the present study and those for lumbar discs derived in previous studies. CONCLUSIONS: The HDS was confirmed to be as accurate in predicting the degree of degeneration in the cervical spine as in the lumbar region. To our best knowledge, this is the first reported and validated histological classification system intended for assessing histological degeneration in the cervical spine. Therefore, HDS can be recommended for academic and pathologic purposes in cervical disc degeneration.