Mepe, short for matrix extracellular phosphoglycoprotein, belongs to the SIBLING protein family. It plays a crucial role in regulating systemic phosphate homeostasis and mineralization, being part of a hormone/enzyme/extracellular matrix protein cascade involving FGF23 and PHEX [1,3,5]. It is also involved in craniofacial and dental matrix maturation, potentially maintaining non-mineralized matrix [2].

Analysis of Mepe null mouse molars showed increased thickness of predentin, dentin, and enamel, along with decreased gene expression of Enam, Bsp, Dmp1, Dspp, and Opn [2]. In addition, a loss-of-function (LoF) mutation in MEPE in human studies was associated with decreased ultradistal forearm bone mineral density (BMD), increased osteoporosis, and fracture risk, which was further evaluated in UK and Icelandic samples [4].

In conclusion, Mepe is essential for phosphate homeostasis, mineralization in bones and teeth. The Mepe null mouse model and human LoF studies have revealed its role in maintaining proper dental and bone structure, and its implications in osteoporosis and fracture-related diseases.

References:

1. Quarles, L Darryl. . FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. In American journal of physiology. Endocrinology and metabolism, 285, E1-9. doi:. https://pubmed.ncbi.nlm.nih.gov/12791601/

2. Gullard, Angela, Gluhak-Heinrich, Jelica, Papagerakis, Silvana, Chen, Shuo, MacDougall, Mary. 2016. MEPE Localization in the Craniofacial Complex and Function in Tooth Dentin Formation. In The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 64, 224-36. doi:10.1369/0022155416635569. https://pubmed.ncbi.nlm.nih.gov/26927967/

3. Rowe, Peter S N. 2004. The wrickkened pathways of FGF23, MEPE and PHEX. In Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists, 15, 264-81. doi:. https://pubmed.ncbi.nlm.nih.gov/15470265/

4. Surakka, Ida, Fritsche, Lars G, Zhou, Wei, Hveem, Kristian, Willer, Cristen J. 2020. MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk. In Nature communications, 11, 4093. doi:10.1038/s41467-020-17315-0. https://pubmed.ncbi.nlm.nih.gov/33097703/

5. Rowe, Peter S N. . Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway. In Critical reviews in eukaryotic gene expression, 22, 61-86. doi:. https://pubmed.ncbi.nlm.nih.gov/22339660/