Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton

K.M. Spoorendonk, J. Peterson-Maduro, J. Renn, T. Trowe, S. Kranenbarg, C. Winkler, S. Schulte-Merker

Research output: Contribution to journalArticleAcademicpeer-review

134 Citations (Scopus)

Abstract

Retinoic acid (RA) plays important roles in diverse biological processes ranging from germ cell specification to limb patterning. RA ultimately exerts its effect in the nucleus, but how RA levels are being generated and maintained locally is less clear. Here, we have analyzed the zebrafish stocksteif mutant, which exhibits severe over-ossification of the entire vertebral column. stocksteif encodes cyp26b1, a cytochrome P450 member that metabolizes RA. The mutant is completely phenocopied by treating 4 dpf wild-type embryos with either RA or the pharmacological Cyp26 blocker R115866, thus identifying a previously unappreciated role for RA and cyp26b1 in osteogenesis of the vertebral column. Cyp26b1 is expressed within osteoblast cells, demonstrating that RA levels within these cells need to be tightly controlled. Furthermore, we have examined the effect of RA on osteoblasts in vivo. As numbers of osteoblasts do not change upon RA treatment, we suggest that RA causes increased activity of axial osteoblasts, ultimately resulting in defective skeletogenesis
LanguageEnglish
Pages3765-3774
JournalDevelopment
Volume135
Issue number21
DOIs
Publication statusPublished - 2008

Fingerprint

Tretinoin
Osteogenesis
Skeleton
Osteoblasts
R 115866
Spine
Biological Phenomena
Zebrafish
Germ Cells
Cytochrome P-450 Enzyme System
Embryonic Structures
Extremities
Pharmacology

Keywords

  • zebrafish early development
  • oryzias-latipes
  • danio-rerio
  • osteoblast differentiation
  • metabolizing enzyme
  • transgenic fish
  • nervous-system
  • expression
  • bone
  • gene

Cite this

Spoorendonk, K. M., Peterson-Maduro, J., Renn, J., Trowe, T., Kranenbarg, S., Winkler, C., & Schulte-Merker, S. (2008). Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. Development, 135(21), 3765-3774. https://doi.org/10.1242/dev.024034
Spoorendonk, K.M. ; Peterson-Maduro, J. ; Renn, J. ; Trowe, T. ; Kranenbarg, S. ; Winkler, C. ; Schulte-Merker, S. / Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. In: Development. 2008 ; Vol. 135, No. 21. pp. 3765-3774.
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abstract = "Retinoic acid (RA) plays important roles in diverse biological processes ranging from germ cell specification to limb patterning. RA ultimately exerts its effect in the nucleus, but how RA levels are being generated and maintained locally is less clear. Here, we have analyzed the zebrafish stocksteif mutant, which exhibits severe over-ossification of the entire vertebral column. stocksteif encodes cyp26b1, a cytochrome P450 member that metabolizes RA. The mutant is completely phenocopied by treating 4 dpf wild-type embryos with either RA or the pharmacological Cyp26 blocker R115866, thus identifying a previously unappreciated role for RA and cyp26b1 in osteogenesis of the vertebral column. Cyp26b1 is expressed within osteoblast cells, demonstrating that RA levels within these cells need to be tightly controlled. Furthermore, we have examined the effect of RA on osteoblasts in vivo. As numbers of osteoblasts do not change upon RA treatment, we suggest that RA causes increased activity of axial osteoblasts, ultimately resulting in defective skeletogenesis",
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Spoorendonk, KM, Peterson-Maduro, J, Renn, J, Trowe, T, Kranenbarg, S, Winkler, C & Schulte-Merker, S 2008, 'Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton', Development, vol. 135, no. 21, pp. 3765-3774. https://doi.org/10.1242/dev.024034

Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. / Spoorendonk, K.M.; Peterson-Maduro, J.; Renn, J.; Trowe, T.; Kranenbarg, S.; Winkler, C.; Schulte-Merker, S.

In: Development, Vol. 135, No. 21, 2008, p. 3765-3774.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Spoorendonk, K.M.

AU - Peterson-Maduro, J.

AU - Renn, J.

AU - Trowe, T.

AU - Kranenbarg, S.

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AU - Schulte-Merker, S.

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