Human MEPE/OF45 Antibody

MEPE (matrix extracellular phosphoglycoprotein), known as OF45 in mouse and rat, is a 55 kDa member of the SIBLING protein family. MEPE is primarily expressed in bone and dentin, where it regulates the mineralization of those tissues (1‑3). The human MEPE cDNA encodes a 525 amino acid (aa) precursor that includes a 17 aa signal sequence. MEPE contains multiple consensus sites for post-translational modifications, including N-linked glycosylation, N-myristoylation, glycosaminoglycan attachment, and phosphorylation by a variety of kinases. MEPE also contains several putative proteolytic cleavage sites and one integrin-binding RGD motif (3, 4). There is therefore considerable potential for post-translational regulation of MEPE function and its degradation products. MEPE is secreted by osteoblasts and dental pulp stem cells during the mineralization process (5‑7) and also by nonmineralizing tissues including epithelial cells in the renal proximal tubule and salivary duct (8, 9). MEPE has an inhibitory function in bone formation, (5) although a peptide corresponding to aa 242‑264 stimulates new bone formation and the proliferation of osteoblasts and dental pulp stem cells (10, 11). MEPE contains one C‑terminal ASARM motif common to SIBLING proteins. Similar to intact MEPE, the ASARM peptide inhibits bone mineralization and plays a central role in the phosphaturia and reduced mineralization of X-linked hypophosphatemic rickets (HYP) and tumor‑induced osteomalacia (TIO) (12, 13). The zinc metalloprotease Phex binds directly to MEPE via the ASARM motif and prevents ASARM cleavage (13, 14). Multiple inactivating mutations in Phex are found in HYP and TIO and result in the increased liberation of ASARM peptide (15). Both MEPE and ASARM peptide are elevated in these disorders of mineralization and phosphate metabolism (12).