Oral Citrate Supplementation Mitigates Age-Associated Pathologic Intervertebral Disc Calcification in LG/J Mice

Area of Science:

• Biomedical research
• Skeletal biology
• Pharmacology

Background:

• Age-dependent intervertebral disc calcification is prevalent and lacks effective treatments.
• LG/J mice exhibit spontaneous, age-associated disc calcification, serving as a relevant model.
• Understanding the mechanisms of disc calcification is crucial for developing therapeutic interventions.

Purpose of the Study:

• To evaluate the efficacy of long-term oral potassium citrate (K3Citrate) supplementation in ameliorating intervertebral disc calcification in LG/J mice.
• To investigate the impact of K3Citrate on vertebral bone structure, knee calcification, plasma chemistry, and locomotion.
• To elucidate the mechanistic effects of K3Citrate on cellular differentiation and mineral composition within the intervertebral disc.

Main Methods:

• Long-term oral administration of K3Citrate to LG/J mice.
• Assessment of disc calcification incidence and severity.
• Analysis of vertebral bone structure, knee calcification, plasma chemistry, and locomotion.
• Fourier-transform infrared (FTIR) spectroscopy to analyze mineral composition.
• Evaluation of endochondral differentiation in nucleus pulposus (NP) and endplate cells.

Main Results:

• K3Citrate significantly reduced the incidence of intervertebral disc calcification.
• No adverse effects were observed on vertebral bone structure, knee calcification, plasma chemistry, or general locomotion.
• Treated mice showed improved grip strength.
• FTIR analysis confirmed K3Citrate did not alter the mineral composition of calcified nodules.
• K3Citrate mitigated calcification by chelating Ca2+ and differentially affected cell differentiation, reducing hypertrophic chondrocytic fate in NP cells but not impacting endplates.

Conclusions:

• Oral K3Citrate is a promising systemic intervention for age-dependent intervertebral disc calcification.
• The therapeutic effect involves Ca2+ chelation and modulation of NP cell differentiation.
• K3Citrate ameliorates disc calcification without compromising skeletal integrity or general physical function.