| Autor: |
Ottone OK; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, PA, USA., Mundo JJ; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Kwakye BN; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Slaweski A; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Collins JA; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Wu Q; LabCorp, Morrisville, NC, USA., Connelly MA; LabCorp, Morrisville, NC, USA., Niaziorimi F; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.; PXE International Center of Excellence for Research and Clinical Care., van de Wetering K; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.; PXE International Center of Excellence for Research and Clinical Care., Risbud MV; Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.; Graduate Program in Cell Biology and Regenerative Medicine, Jefferson College of Life Sciences, Thomas Jefferson University, Philadelphia, PA, USA. |
| Abstrakt: |
Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate 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 successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion. Notably, a positive effect on grip strength was evident in treated mice. Spectroscopic investigation of the persisting calcified nodules indicated K 3 Citrate did not alter the mineral composition and revealed that reactivation of an endochondral differentiation program in endplates may drive LG/J disc calcification. Importantly, K 3 Citrate reduced calcification incidence without altering the pathological endplate chondrocyte hypertrophy, suggesting mitigation of disc calcification primarily occurred through Ca 2+ chelation, a conclusion supported by chondrogenic differentiation and Seahorse metabolic assays. Overall, this study underscores the therapeutic potential of K 3 Citrate as a systemic intervention strategy for disc calcification. |
