MatrixGlaProtein

Matrix Gla Protein (MGP) is a small secreted, vitamin K–dependent extracellular matrix protein found in cartilage and vascular tissues. It is produced by chondrocytes and vascular smooth muscle cells and requires gamma-carboxylation of several glutamate residues to become active. The gamma-carboxylated form is secreted into the extracellular matrix where it can participate in mineralization control.

Functionally, MGP inhibits soft-tissue calcification by binding calcium ions and inhibiting hydroxyapatite crystal formation; it may also antagonize bone morphogenetic protein signaling to restrain mineral deposition in tissues.

Regulation and forms: The biological activity of MGP depends on vitamin K–dependent gamma-carboxylation. Uncarboxylated MGP (ucMGP) is inactive; desphospho-uncarboxylated MGP (dp-ucMGP) is measured in plasma as a biomarker of vitamin K status and vascular calcification risk. Warfarin and other vitamin K antagonists reduce MGP carboxylation, potentially increasing calcification risk.

Clinical significance and research: Lower MGP activity has been linked with vascular calcification in aging, chronic kidney disease, and diabetes. MGP expression is studied as a biomarker and therapeutic target; trials have explored vitamin K supplementation to improve MGP carboxylation, though clinical benefits for vascular outcomes remain under investigation.