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Fibrous Dysplasia and Fibroblast Growth Factor-23 Regulation

  • Skeletal Biology (DB Burr, Section Editor)
  • Published:
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Abstract

Fibrous dysplasia (FD) is a skeletal disorder caused by activating mutations in Gsα that result in elevations in cAMP. A feature of FD is elevated blood levels of the bone cell-derived phosphaturic hormone, fibroblast growth factor-23 (FGF23). FGF23 regulates serum phosphorus and active vitamin D levels by action on proximal renal tubule cells. An essential step in the production of biologically active FGF23 is glycosylation by the UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T3). In the absence of glycosylation, FGF23 is processed into inactive N- and C-terminal proteins by a subtilisin proprotein convertase, probably furin. Normally, most if not all circulating FGF23 is intact. In FD, C-terminal levels are elevated, suggesting altered FGF23 processing. Altered processing in FD is the result of a cAMP-dependent, coordinated decrease in ppGalNAc-T3 and an increase in furin enzyme activity. These findings, and emerging data from other diseases, suggest regulation of FGF23 processing may be a physiologically important process.

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Acknowledgment

This manuscript was supported by Division of Intramural Research of the National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human services (A.M.B., N.B., and M.T.C.), and the Bone Health Program at Children’s National Medical Center (A.M.B.).

Disclosure

A.M. Boyce declares no conflicts of interest. N. Bhattacharyya declares no conflicts of interest. M.T. Collins declares no conflicts of interest.

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  1. Bone Health Program, Division of Orthopaedics and Sports Medicine, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC, 20010, USA

    Alison M. Boyce

  2. Division of Endocrinology and Diabetes, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC, 20010, USA

    Alison M. Boyce

  3. Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Building 30, Room 228, MSC 4320, Bethesda, MD, 20892-4320, USA

    Nisan Bhattacharyya & Michael T. Collins

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Boyce, A.M., Bhattacharyya, N. & Collins, M.T. Fibrous Dysplasia and Fibroblast Growth Factor-23 Regulation. Curr Osteoporos Rep 11, 65–71 (2013). https://doi.org/10.1007/s11914-013-0144-5

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