Implication of a novel vitamin K dependent protein, GRP/Ucma in the pathophysiological conditions associated with vascular and soft tissue calcification, osteoarthritis, inflammation, and carcinoma

Gla-rich protein (GRP) or unique cartilage matrix-associated protein (Ucma), the newest member of vitamin K dependent proteins, carries exceptionally high number of γ-carboxyglutamic acid (Gla) residues which contributes to its outstanding capacity of binding with calcium in the extracellular environment indicating its potential role as a global calcium modulator. Recent studies demonstrated a critical function of GRP in the regulation of different pathophysiological conditions associated with vascular and soft tissue calcification including cardiovascular diseases, osteoarthritis, inflammation, and skin and breast carcinomas. These findings established an important relationship between γ-carboxylation of GRP and calcification associated disease pathology suggesting a critical role of vitamin K in the pathophysiological features of various health disorders. This review for the first time summarizes all of the updated findings related to the functional activities of GRP in the pathogenesis of several diseases associated with vascular and soft tissue mineralization, osteoarthritis, inflammation, and carcinoma. The outcome of this review will improve the understanding about the role of GRP in the pathogenesis of tissue calcification and its associated health disorders, which should in turn lead to the design of clinical interventions to improve the condition of patients associated with these health disorders.