C-terminal but not intact fibroblast growth factor 23 levels

Vanessa M. Knab, Braden Corbin, Olena Andrukhova, Julia M. Hum, Pu Ni, Seham Rabadi, Akira Maeda, Kenneth White, Reinhold G. Erben, Harald Jüppner, Marta Christov

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The acute effects of parathyroid hormone (PTH) on fibroblast growth factor 23 (FGF23) in vivo are not well understood. After a single subcutaneous PTH (1-34) injection (50 nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/ C-terminal FGF23 (cFGF23). Furthermore, FGF23 messenger RNA (mRNA) and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by three- to fivefold within 2 hours following PTH injection, which returned to baseline by 4 hours. In contrast, iFGF23 levels remained unchanged for the first 2 hours, yet declined to ;60% by 6 hours and remained suppressed before returning to baseline after 24 hours. Using homozygous mice for an autosomal dominant hypophosphatemic rickets-FGF23 mutation or animals treated with a furin inhibitor, we showed that cFGF23 and iFGF23 levels increased equivalently after PTH injection. These findings are consistent with increased FGF23 production in bone, yet rapid cleavage of the secreted intact protein. Using primary osteocyte-like cell cultures, we showed that PTH increased FGF23 mRNA expression through cyclic adenosine monophosphate/protein kinase A, but not inositol triphosphate/protein kinase C signaling; PTH also increased furin protein levels. In conclusion, PTH injection rapidly increases FGF23 production in bone in vivo and in vitro. However, iFGF23 is rapidly degraded. At later time points through an unidentified mechanism, a sustained decrease in FGF23 production occurs.

Original languageEnglish (US)
Pages (from-to)1130-1139
Number of pages10
JournalEndocrinology
Volume158
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Parathyroid Hormone
Furin
Osteocytes
Injections
Bone and Bones
fibroblast growth factor 23
Messenger RNA
Inositol
Cyclic AMP-Dependent Protein Kinases
Cyclic AMP
Protein Kinase C
Proteins
Cell Culture Techniques
Mutation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Knab, V. M., Corbin, B., Andrukhova, O., Hum, J. M., Ni, P., Rabadi, S., ... Christov, M. (2017). C-terminal but not intact fibroblast growth factor 23 levels. Endocrinology, 158(5), 1130-1139. https://doi.org/10.1210/en.2016-1451

C-terminal but not intact fibroblast growth factor 23 levels. / Knab, Vanessa M.; Corbin, Braden; Andrukhova, Olena; Hum, Julia M.; Ni, Pu; Rabadi, Seham; Maeda, Akira; White, Kenneth; Erben, Reinhold G.; Jüppner, Harald; Christov, Marta.

In: Endocrinology, Vol. 158, No. 5, 01.05.2017, p. 1130-1139.

Research output: Contribution to journalArticle

Knab, VM, Corbin, B, Andrukhova, O, Hum, JM, Ni, P, Rabadi, S, Maeda, A, White, K, Erben, RG, Jüppner, H & Christov, M 2017, 'C-terminal but not intact fibroblast growth factor 23 levels', Endocrinology, vol. 158, no. 5, pp. 1130-1139. https://doi.org/10.1210/en.2016-1451
Knab VM, Corbin B, Andrukhova O, Hum JM, Ni P, Rabadi S et al. C-terminal but not intact fibroblast growth factor 23 levels. Endocrinology. 2017 May 1;158(5):1130-1139. https://doi.org/10.1210/en.2016-1451
Knab, Vanessa M. ; Corbin, Braden ; Andrukhova, Olena ; Hum, Julia M. ; Ni, Pu ; Rabadi, Seham ; Maeda, Akira ; White, Kenneth ; Erben, Reinhold G. ; Jüppner, Harald ; Christov, Marta. / C-terminal but not intact fibroblast growth factor 23 levels. In: Endocrinology. 2017 ; Vol. 158, No. 5. pp. 1130-1139.
@article{99029c4be7044f1498f74f8ca73cbad2,
title = "C-terminal but not intact fibroblast growth factor 23 levels",
abstract = "The acute effects of parathyroid hormone (PTH) on fibroblast growth factor 23 (FGF23) in vivo are not well understood. After a single subcutaneous PTH (1-34) injection (50 nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/ C-terminal FGF23 (cFGF23). Furthermore, FGF23 messenger RNA (mRNA) and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by three- to fivefold within 2 hours following PTH injection, which returned to baseline by 4 hours. In contrast, iFGF23 levels remained unchanged for the first 2 hours, yet declined to ;60{\%} by 6 hours and remained suppressed before returning to baseline after 24 hours. Using homozygous mice for an autosomal dominant hypophosphatemic rickets-FGF23 mutation or animals treated with a furin inhibitor, we showed that cFGF23 and iFGF23 levels increased equivalently after PTH injection. These findings are consistent with increased FGF23 production in bone, yet rapid cleavage of the secreted intact protein. Using primary osteocyte-like cell cultures, we showed that PTH increased FGF23 mRNA expression through cyclic adenosine monophosphate/protein kinase A, but not inositol triphosphate/protein kinase C signaling; PTH also increased furin protein levels. In conclusion, PTH injection rapidly increases FGF23 production in bone in vivo and in vitro. However, iFGF23 is rapidly degraded. At later time points through an unidentified mechanism, a sustained decrease in FGF23 production occurs.",
author = "Knab, {Vanessa M.} and Braden Corbin and Olena Andrukhova and Hum, {Julia M.} and Pu Ni and Seham Rabadi and Akira Maeda and Kenneth White and Erben, {Reinhold G.} and Harald J{\"u}ppner and Marta Christov",
year = "2017",
month = "5",
day = "1",
doi = "10.1210/en.2016-1451",
language = "English (US)",
volume = "158",
pages = "1130--1139",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "5",

}

TY - JOUR

T1 - C-terminal but not intact fibroblast growth factor 23 levels

AU - Knab, Vanessa M.

AU - Corbin, Braden

AU - Andrukhova, Olena

AU - Hum, Julia M.

AU - Ni, Pu

AU - Rabadi, Seham

AU - Maeda, Akira

AU - White, Kenneth

AU - Erben, Reinhold G.

AU - Jüppner, Harald

AU - Christov, Marta

PY - 2017/5/1

Y1 - 2017/5/1

N2 - The acute effects of parathyroid hormone (PTH) on fibroblast growth factor 23 (FGF23) in vivo are not well understood. After a single subcutaneous PTH (1-34) injection (50 nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/ C-terminal FGF23 (cFGF23). Furthermore, FGF23 messenger RNA (mRNA) and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by three- to fivefold within 2 hours following PTH injection, which returned to baseline by 4 hours. In contrast, iFGF23 levels remained unchanged for the first 2 hours, yet declined to ;60% by 6 hours and remained suppressed before returning to baseline after 24 hours. Using homozygous mice for an autosomal dominant hypophosphatemic rickets-FGF23 mutation or animals treated with a furin inhibitor, we showed that cFGF23 and iFGF23 levels increased equivalently after PTH injection. These findings are consistent with increased FGF23 production in bone, yet rapid cleavage of the secreted intact protein. Using primary osteocyte-like cell cultures, we showed that PTH increased FGF23 mRNA expression through cyclic adenosine monophosphate/protein kinase A, but not inositol triphosphate/protein kinase C signaling; PTH also increased furin protein levels. In conclusion, PTH injection rapidly increases FGF23 production in bone in vivo and in vitro. However, iFGF23 is rapidly degraded. At later time points through an unidentified mechanism, a sustained decrease in FGF23 production occurs.

AB - The acute effects of parathyroid hormone (PTH) on fibroblast growth factor 23 (FGF23) in vivo are not well understood. After a single subcutaneous PTH (1-34) injection (50 nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/ C-terminal FGF23 (cFGF23). Furthermore, FGF23 messenger RNA (mRNA) and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by three- to fivefold within 2 hours following PTH injection, which returned to baseline by 4 hours. In contrast, iFGF23 levels remained unchanged for the first 2 hours, yet declined to ;60% by 6 hours and remained suppressed before returning to baseline after 24 hours. Using homozygous mice for an autosomal dominant hypophosphatemic rickets-FGF23 mutation or animals treated with a furin inhibitor, we showed that cFGF23 and iFGF23 levels increased equivalently after PTH injection. These findings are consistent with increased FGF23 production in bone, yet rapid cleavage of the secreted intact protein. Using primary osteocyte-like cell cultures, we showed that PTH increased FGF23 mRNA expression through cyclic adenosine monophosphate/protein kinase A, but not inositol triphosphate/protein kinase C signaling; PTH also increased furin protein levels. In conclusion, PTH injection rapidly increases FGF23 production in bone in vivo and in vitro. However, iFGF23 is rapidly degraded. At later time points through an unidentified mechanism, a sustained decrease in FGF23 production occurs.

UR - http://www.scopus.com/inward/record.url?scp=85019141674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019141674&partnerID=8YFLogxK

U2 - 10.1210/en.2016-1451

DO - 10.1210/en.2016-1451

M3 - Article

C2 - 28324013

AN - SCOPUS:85019141674

VL - 158

SP - 1130

EP - 1139

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 5

ER -