Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility

Keith G. Avin, Julian A. Vallejo, Xuening (Neal) Chen, Kun Wang, Chad D. Touchberry, Marco Brotto, Sarah L. Dallas, Sharon Moe, Michael J. Wacker

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Skeletal muscle dysfunction accompanies the clinical disorders of chronic kidney disease (CKD) and hereditary hypophosphatemic rickets. In both disorders, fibroblast growth factor 23 (FGF23), a bone-derived hormone regulating phosphate and vitamin D metabolism, becomes chronically elevated. FGF23 has been shown to play a direct role in cardiac muscle dysfunction; however, it is unknown whether FGF23 signaling can also directly induce skeletal muscle dysfunction. We found expression of potential FGF23 receptors (Fgfr1–4) and α-Klotho in muscles of two animal models (CD-1 and Cy/< rat, a naturally occurring rat model of chronic kidney disease-mineral bone disorder) as well as C2C12 myoblasts and myotubes. C2C12 proliferation, myogenic gene expression, oxidative stress marker 8-OHdG, intracellular Ca2+ ([Ca2+]i), and ex vivo contractility of extensor digitorum longus (EDL) or soleus muscles were assessed after treatment with various amounts of FGF23. FGF23 (2–100 ng/ml) did not alter C2C12 proliferation, expression of myogenic genes, or oxidative stress after 24-to 72-h treatment. Acute or prolonged FGF23 treatment up to 6 days did not alter C2C12 [Ca2+]i handling, nor did acute treatment with FGF23 (9–100 ng/ml) affect EDL and soleus muscle contractility. In conclusion, although skeletal muscles express the receptors involved in FGF23-mediated signaling, in vitro FGF23 treatments failed to directly alter skeletal muscle development or function under the conditions tested. We hypothesize that other endogenous substances may be required to act in concert with FGF23 or apart from FGF23 to promote muscle dysfunction in hereditary hypophosphatemic rickets and CKD.

Original languageEnglish (US)
Pages (from-to)E594-E604
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume315
Issue number4
DOIs
StatePublished - Oct 2 2018

Fingerprint

Muscle Cells
Cell Differentiation
Skeletal Muscle
Cell Proliferation
Muscles
Familial Hypophosphatemic Rickets
Chronic Renal Insufficiency
fibroblast growth factor 23
Oxidative Stress
Chronic Kidney Disease-Mineral and Bone Disorder
Gene Expression
Fibroblast Growth Factor Receptors
Muscle Development
Myoblasts
Skeletal Muscle Fibers
Vitamin D
Myocardium
Animal Models
Phosphates
Hormones

Keywords

  • Chronic kidney disease
  • Fibroblast growth factor 23
  • Hypophosphatemic rickets
  • Intracellular Ca
  • Myogenesis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility. / Avin, Keith G.; Vallejo, Julian A.; Chen, Xuening (Neal); Wang, Kun; Touchberry, Chad D.; Brotto, Marco; Dallas, Sarah L.; Moe, Sharon; Wacker, Michael J.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 315, No. 4, 02.10.2018, p. E594-E604.

Research output: Contribution to journalArticle

Avin, Keith G. ; Vallejo, Julian A. ; Chen, Xuening (Neal) ; Wang, Kun ; Touchberry, Chad D. ; Brotto, Marco ; Dallas, Sarah L. ; Moe, Sharon ; Wacker, Michael J. / Fibroblast growth factor 23 does not directly influence skeletal muscle cell proliferation and differentiation or ex vivo muscle contractility. In: American Journal of Physiology - Endocrinology and Metabolism. 2018 ; Vol. 315, No. 4. pp. E594-E604.
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abstract = "Skeletal muscle dysfunction accompanies the clinical disorders of chronic kidney disease (CKD) and hereditary hypophosphatemic rickets. In both disorders, fibroblast growth factor 23 (FGF23), a bone-derived hormone regulating phosphate and vitamin D metabolism, becomes chronically elevated. FGF23 has been shown to play a direct role in cardiac muscle dysfunction; however, it is unknown whether FGF23 signaling can also directly induce skeletal muscle dysfunction. We found expression of potential FGF23 receptors (Fgfr1–4) and α-Klotho in muscles of two animal models (CD-1 and Cy/< rat, a naturally occurring rat model of chronic kidney disease-mineral bone disorder) as well as C2C12 myoblasts and myotubes. C2C12 proliferation, myogenic gene expression, oxidative stress marker 8-OHdG, intracellular Ca2+ ([Ca2+]i), and ex vivo contractility of extensor digitorum longus (EDL) or soleus muscles were assessed after treatment with various amounts of FGF23. FGF23 (2–100 ng/ml) did not alter C2C12 proliferation, expression of myogenic genes, or oxidative stress after 24-to 72-h treatment. Acute or prolonged FGF23 treatment up to 6 days did not alter C2C12 [Ca2+]i handling, nor did acute treatment with FGF23 (9–100 ng/ml) affect EDL and soleus muscle contractility. In conclusion, although skeletal muscles express the receptors involved in FGF23-mediated signaling, in vitro FGF23 treatments failed to directly alter skeletal muscle development or function under the conditions tested. We hypothesize that other endogenous substances may be required to act in concert with FGF23 or apart from FGF23 to promote muscle dysfunction in hereditary hypophosphatemic rickets and CKD.",
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AU - Avin, Keith G.

AU - Vallejo, Julian A.

AU - Chen, Xuening (Neal)

AU - Wang, Kun

AU - Touchberry, Chad D.

AU - Brotto, Marco

AU - Dallas, Sarah L.

AU - Moe, Sharon

AU - Wacker, Michael J.

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AB - Skeletal muscle dysfunction accompanies the clinical disorders of chronic kidney disease (CKD) and hereditary hypophosphatemic rickets. In both disorders, fibroblast growth factor 23 (FGF23), a bone-derived hormone regulating phosphate and vitamin D metabolism, becomes chronically elevated. FGF23 has been shown to play a direct role in cardiac muscle dysfunction; however, it is unknown whether FGF23 signaling can also directly induce skeletal muscle dysfunction. We found expression of potential FGF23 receptors (Fgfr1–4) and α-Klotho in muscles of two animal models (CD-1 and Cy/< rat, a naturally occurring rat model of chronic kidney disease-mineral bone disorder) as well as C2C12 myoblasts and myotubes. C2C12 proliferation, myogenic gene expression, oxidative stress marker 8-OHdG, intracellular Ca2+ ([Ca2+]i), and ex vivo contractility of extensor digitorum longus (EDL) or soleus muscles were assessed after treatment with various amounts of FGF23. FGF23 (2–100 ng/ml) did not alter C2C12 proliferation, expression of myogenic genes, or oxidative stress after 24-to 72-h treatment. Acute or prolonged FGF23 treatment up to 6 days did not alter C2C12 [Ca2+]i handling, nor did acute treatment with FGF23 (9–100 ng/ml) affect EDL and soleus muscle contractility. In conclusion, although skeletal muscles express the receptors involved in FGF23-mediated signaling, in vitro FGF23 treatments failed to directly alter skeletal muscle development or function under the conditions tested. We hypothesize that other endogenous substances may be required to act in concert with FGF23 or apart from FGF23 to promote muscle dysfunction in hereditary hypophosphatemic rickets and CKD.

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KW - Hypophosphatemic rickets

KW - Intracellular Ca

KW - Myogenesis

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