Intervertebral disc degeneration : symptomatic and asymptomatic distinguishers
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Introduction: It is currently not possible to distinguish symptomatic (S) from asymptomatic (A) intervertebral disc degeneration (IVDD) based on patient factors or the degree of degeneration. Additionally, it is not known if age, sex, and BMI contribute to the gross/radiographic or histological progression of IVDD. These studies were performed to determine patient, gross/radiographic, histological, and protein differentiators of S-IVDD or A-IVDD. Methods: IVD tissues were recovered from 202 S clinical patients and 36 A tissue donors with IRB Approval (#2010692), informed patient consent, or a legal permit under the Uniform Anatomical Gift Act as appropriate. Age, sex, BMI, Pfirrmann grade, Thompson grade, and histological degeneration scores (HDS) were determined. Each isolated tissue was cultured for 6 days in supplemented DMEM which was collected every 3 days, and tissue culture media were assessed for their content of inflammatory cytokines/chemokines, degradative enzymes (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and growth factors. Gross/radiographic grades, histological scores, and ex vivo biomarker data were compared within and between S-IVD and A-IVDs using multivariable generalized linear models or ANOVAs while adjusting for age, sex, and BMI as covariates with significance set at p<0.05. Results: Overall, S-IVDs produced significantly increased levels of inflammatory cytokines/chemokines, specific degradative enzymes, and lower levels of TIMPs compared to A-IVDs regardless of IVDD severity. Obesity significantly affected the progression of IVDD in S and A populations. Discussion: Obesity and inflammatory cytokines may represent key factors in distinguishing S-IVDD versus A-IVDD towards earlier identification and symptom mitigation in clinical patients.
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Ph. D.