Special Poster Session 51st International Society for the Study of the Lumbar Spine Annual Meeting 2025

Introduction

Obesity and type 2 diabetes mellitus (T2DM) are increasingly recognized as critical contributing factors to musculoskeletal disorders, particularly intervertebral disc degeneration (IDD), which is frequently linked to low back pain (LBP). Despite the previous clinical associations between these metabolic conditions and IDD, the biological mechanisms driving this relationship are not fully understood¹. Recent research has suggested that dysfunction in adipose tissue (AT) among obese individuals may lead to a pro-inflammatory environment in intervertebral disc cells, potentially accelerating IDD. This study investigates the effects of obesity and T2DM-related secretome signaling on IDD progression and nociception using an established IDD mouse model with the aim of clarifying these mechanisms².

Methods

Following approval from the Ethics Committee, we initially co-cultured healthy and degenerative human nucleus pulposus (NP) cells with conditioned media from AT (AT-CM) obtained from individuals with varying body mass indices (BMI), blood glucose levels, and hemoglobin A1c values. We assessed the effects of AT-CM on NP cell behavior through RT-qPCR to evaluate the expression of inflammatory mediators and cell phenotype markers. The in vivo study utilized a surgically induced tail-looping mouse model to simulate IDD due to abnormal mechanical stress³. C57BL/6N mice were assigned to three different dietary groups: chow (Control), high-fat diet (HFD), and a high-fat diet combined with two low doses of streptozotocin to induce T2DM (HFD+T2DM). Over a 16-week period, we tracked body weight, blood glucose levels, radiographic changes, and Grip-force and Von Frey assessments were used for pain-related behavioral changes. Histological, immunohistochemical, and molecular evaluations were conducted on the specimens’ spine.

Results

In vitro analysis revealed that NP cells exposed to AT-CM from obese patients exhibited an increase in TNFα, leptin, and lipocalin 2 levels, pointing to a heightened inflammatory state. The mouse model demonstrated significantly more IDD in the high-fat diet and diabetic groups, indicated by a lower disc height index (DHI) and more pronounced histological degeneration, in coccygeal discs in either the tail-loop or at the tail base level (not subjected to mechanical stress), compared to the chow diet group. Behavioral tests confirmed greater mechanical hypersensitivity and reduced grip strength in the obese and diabetic mice, reflecting an exacerbation of nociceptive responses under these metabolic conditions. 

Discussion

The results from both studies underscore the detrimental effects of obesity and T2DM on the progression of IDD. The co-culture findings provide important insights into the paracrine interactions between dysfunctional adipose tissue and NP cells, while the murine model provides further outcomes showing enhanced IDD and nociception in the obese and diabetic groups. These findings emphasize that metabolic disorders significantly contribute to disc degeneration, promoting not only structural damage but also heightened pain sensitivity. Future research, including additional histological and immunohistochemical analyses, will further quantify these observations and explore the underlying mechanisms linking obesity and T2DM to IDD progression.