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

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. We investigated the efficacy of long-term oral K(3)Citrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. K(3)Citrate reduced the incidence of disc calcification without affecting the vertebral bone structure, knee calcification, plasma chemistry, or locomotion in LG/J mice. Notably, a positive effect on grip strength was evident in treated mice. FTIR spectroscopy of the persisting calcified nodules indicated K(3)Citrate did not alter the mineral composition. Mechanistically, activation of an endochondral differentiation in the cartilaginous endplates and nucleus pulposus (NP) compartment contributed to LG/J disc calcification. Importantly, K(3)Citrate reduced calcification incidence by Ca(2+) chelation throughout the disc while exhibiting a differential effect on NP and endplate cell differentiation. In the NP compartment, K(3)Citrate reduced the NP cell acquisition of a hypertrophic chondrocytic fate, but the pathologic endochondral program was unimpacted in the endplates. Overall, this study for the first time shows the therapeutic potential of oral K(3)Citrate as a systemic intervention strategy to ameliorate disc calcification.