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A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.

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Glucose concentration modulates bovine intervertebral disc response under physiological loading.

D Zuncheddu^1,2, M Muerner^1,3, K Klavins^4,5

¹AO Research Institute Davos, Davos, Switzerland.

Frontiers in Bioengineering and Biotechnology

|April 13, 2026

Summary

Optimizing glucose levels in ex vivo intervertebral disc (IVD) cultures is crucial for accurate research. Lower glucose significantly reduces cell viability, with some sex-dependent metabolic responses observed in bovine IVD models.

Keywords:

ex vivo glucose metabolism intervertebral disc mechanical loading organ culture sex differences

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Area of Science:

Biomedical Engineering
Cell Biology
Connective Tissue Research

Background:

Ex vivo organ culture is a standard model for intervertebral disc (IVD) research.
Current IVD culture methods often use high glucose concentrations (25 mM) not reflective of physiological conditions.
Emerging evidence suggests sex-based differences in connective tissue diseases warrant investigation in IVD models.

Purpose of the Study:

To investigate the impact of varying glucose concentrations on bovine IVD organ cultures.
To determine if sex influences the response of IVD cells to different glucose levels.
To assess cell viability, metabolism, and marker expression under varied glucose conditions.

Main Methods:

Bovine IVDs were cultured in a bioreactor under physiological loading for one week.
Cultures were supplemented with varying glucose concentrations: 25 mM, 11 mM, and 5.5 mM.
Analyses included cell viability, glycosaminoglycan (GAG) release, disc height, and expression of metabolic, anabolic, and catabolic markers.

Main Results:

Reduced glucose concentrations (11 mM and 5.5 mM) significantly decreased IVD cell viability compared to 25 mM.
Metabolomic analysis indicated adaptive responses to the ex vivo environment at lower glucose levels.
While overall cell viability showed no sex difference, males exhibited higher apoptotic marker expression in the nucleus pulposus (NP) at 5.5 mM glucose. Anabolic and glucose transporter markers also showed sex-dependent expression.

Conclusions:

Glucose concentration critically affects bovine IVD cell viability and metabolism in ex vivo cultures.
The study highlights the need for optimized nutrient conditions in IVD organ culture models to better mimic in vivo physiology.
Sex-specific responses to glucose levels underscore the importance of considering sex in IVD research and treatment development.