Bone and heart health in chronic kidney disease: role of dentin matrix protein 1.

ABSTRACT

PURPOSE OF REVIEW Chronic kidney disease (CKD) is a condition associated with bone disease and fibroblast growth factor 23 (FGF23) excess that contributes to cardiovascular mortality. Dentin matrix protein 1 (DMP1) is an established regulator of bone mineralization and FGF23 production in osteocytes. To date, DMP1 function has mainly been studied in the context of hereditary hypophosphatemic rickets diseases. This review describes the role of DMP1 as a potential strong candidate to prevent bone disorders, FGF23 elevation and associated cardiac outcomes in CKD. RECENT FINDINGS: Patients and mice with CKD show impaired osteocyte maturation and impaired regulation of DMP1 and FGF23 in bone. New data suggest that impaired DMP1 production contributes to CKD-associated bone and mineral metabolism disorders and we show that DMP1 repletion improves osteocyte alterations, bone mineralization and partially prevents FGF23 elevation. As a result, mice with CKD show attenuated left ventricular hypertrophy and improved survival. SUMMARY: There is an urgent need for new therapeutic strategies to improve bone quality and to lower FGF23 levels in CKD. By preventing osteocyte apoptosis and inhibiting Fgf23 transcription, DMP1 supplementation may represent an ideal approach to improve CKD-associated bone and cardiac outcomes.