Matrix extracellular phosphoglycoprotein

Matrix extracellular phosphoglycoprotein (MEPE) is a protein that in humans is encoded by the MEPE gene. This protein is part of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family, which includes other proteins such as osteopontin, bone sialoprotein, dentin matrix protein 1, and dentin sialophosphoprotein. MEPE is predominantly expressed in bone and dental tissues, playing a crucial role in bone mineralization and phosphate homeostasis.

Function

MEPE is involved in the regulation of mineralization and phosphate metabolism in bones and teeth. It acts as an inhibitor of hydroxyapatite formation, thereby affecting bone density and strength. MEPE also has a regulatory role in phosphate homeostasis by its association with the Phosphatonin pathway, influencing the renal handling of phosphate. The protein's RGD (Arg-Gly-Asp) sequence facilitates its interaction with integrins, influencing cell adhesion and signaling.

Clinical Significance

Alterations in MEPE expression or function have been linked to several bone disorders. Overexpression of MEPE can lead to osteomalacia, a condition characterized by softening of the bones due to defective bone mineralization. Conversely, reduced MEPE activity is associated with conditions like osteosclerosis, where increased bone density makes bones abnormally hard. MEPE is also of interest in the study of tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome characterized by overproduction of fibroblast growth factor 23 (FGF23), leading to hypophosphatemia and osteomalacia. MEPE's role in phosphate regulation makes it a potential target for therapeutic intervention in diseases affecting bone mineral density and phosphate metabolism.

Genetics

The MEPE gene is located on chromosome 4q21. It is part of a gene cluster that includes other members of the SIBLING family. The gene encodes a protein of approximately 525 amino acids that undergoes extensive post-translational modifications, including glycosylation, which are critical for its function and interaction with other molecules.

Research Directions

Current research on MEPE is focused on elucidating its precise mechanisms of action in bone and mineral homeostasis and exploring its potential as a biomarker for bone-related diseases. Additionally, there is interest in developing therapeutic agents that can modulate MEPE activity to treat conditions like osteoporosis, osteomalacia, and tumor-induced osteomalacia.

See Also

• Bone mineralization
• Phosphate homeostasis
• SIBLING proteins
• Osteomalacia
• Osteosclerosis