Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix

Marion Anne Cooley, Keerthi Harikrishnan, James A. Oppel, Sloan F. Miler, Jeremy L. Barth, Courtney J. Haycraft, Sakamuri V. Reddy, W. Scott Argraves

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1-deficient mice showed reduced mineralization of both membranous and endochondral bones. MicroCT (μCT) analysis of the calvarial bones (i.e., frontal, parietal and interparietal bones collectively) indicated that bone volume in Fbln1 nulls at neonatal stage P0 were reduced by 22% (p = 0.015). Similarly, Fbln1 null frontal bones showed a 16% (p = 0.035) decrease in bone volume, with a reduction in the interfrontal bone, and a discontinuity in the leading edge of the frontal bone. To determine whether Fbln1 played a role in osteoblast differentiation during bone formation, qPCR was used to measure the effects of Fbln1 deficiency on the expression of Osterix (Osx), a transcription factor essential for osteoblast differentiation. This analysis demonstrated that Osx mRNA was significantly reduced in Fbln1-deficient calvarial bones at developmental stages E16.5 (p = 0.049) and E17.5 (p = 0.022). Furthermore, the ability of Bmp-2 to induce Osx expression was significantly diminished in Fbln1-deficient mouse embryo fibroblasts. Together, these findings indicate that Fbln1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of Bmp signaling.

Original languageEnglish (US)
Pages (from-to)30-38
Number of pages9
JournalBone
Volume69
DOIs
StatePublished - Sep 6 2014
Externally publishedYes

Fingerprint

Osteogenesis
Frontal Bone
Bone and Bones
Osteoblasts
Skull
fibulin
Parietal Bone
X-Ray Microtomography
Extracellular Matrix Proteins
Transcription Factors
Embryonic Structures
Fibroblasts
Staining and Labeling
Lung
Messenger RNA

Keywords

  • Bmp-2
  • Extracellular matrix protein
  • Fibulin-1
  • Osteoblast differentiation
  • Osterix

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Medicine(all)

Cite this

Cooley, M. A., Harikrishnan, K., Oppel, J. A., Miler, S. F., Barth, J. L., Haycraft, C. J., ... Scott Argraves, W. (2014). Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix. Bone, 69, 30-38. https://doi.org/10.1016/j.bone.2014.07.038

Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix. / Cooley, Marion Anne; Harikrishnan, Keerthi; Oppel, James A.; Miler, Sloan F.; Barth, Jeremy L.; Haycraft, Courtney J.; Reddy, Sakamuri V.; Scott Argraves, W.

In: Bone, Vol. 69, 06.09.2014, p. 30-38.

Research output: Contribution to journalArticle

Cooley, MA, Harikrishnan, K, Oppel, JA, Miler, SF, Barth, JL, Haycraft, CJ, Reddy, SV & Scott Argraves, W 2014, 'Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix', Bone, vol. 69, pp. 30-38. https://doi.org/10.1016/j.bone.2014.07.038
Cooley MA, Harikrishnan K, Oppel JA, Miler SF, Barth JL, Haycraft CJ et al. Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix. Bone. 2014 Sep 6;69:30-38. https://doi.org/10.1016/j.bone.2014.07.038
Cooley, Marion Anne ; Harikrishnan, Keerthi ; Oppel, James A. ; Miler, Sloan F. ; Barth, Jeremy L. ; Haycraft, Courtney J. ; Reddy, Sakamuri V. ; Scott Argraves, W. / Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix. In: Bone. 2014 ; Vol. 69. pp. 30-38.
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abstract = "The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1-deficient mice showed reduced mineralization of both membranous and endochondral bones. MicroCT (μCT) analysis of the calvarial bones (i.e., frontal, parietal and interparietal bones collectively) indicated that bone volume in Fbln1 nulls at neonatal stage P0 were reduced by 22{\%} (p = 0.015). Similarly, Fbln1 null frontal bones showed a 16{\%} (p = 0.035) decrease in bone volume, with a reduction in the interfrontal bone, and a discontinuity in the leading edge of the frontal bone. To determine whether Fbln1 played a role in osteoblast differentiation during bone formation, qPCR was used to measure the effects of Fbln1 deficiency on the expression of Osterix (Osx), a transcription factor essential for osteoblast differentiation. This analysis demonstrated that Osx mRNA was significantly reduced in Fbln1-deficient calvarial bones at developmental stages E16.5 (p = 0.049) and E17.5 (p = 0.022). Furthermore, the ability of Bmp-2 to induce Osx expression was significantly diminished in Fbln1-deficient mouse embryo fibroblasts. Together, these findings indicate that Fbln1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of Bmp signaling.",
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AU - Scott Argraves, W.

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AB - The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1-deficient mice showed reduced mineralization of both membranous and endochondral bones. MicroCT (μCT) analysis of the calvarial bones (i.e., frontal, parietal and interparietal bones collectively) indicated that bone volume in Fbln1 nulls at neonatal stage P0 were reduced by 22% (p = 0.015). Similarly, Fbln1 null frontal bones showed a 16% (p = 0.035) decrease in bone volume, with a reduction in the interfrontal bone, and a discontinuity in the leading edge of the frontal bone. To determine whether Fbln1 played a role in osteoblast differentiation during bone formation, qPCR was used to measure the effects of Fbln1 deficiency on the expression of Osterix (Osx), a transcription factor essential for osteoblast differentiation. This analysis demonstrated that Osx mRNA was significantly reduced in Fbln1-deficient calvarial bones at developmental stages E16.5 (p = 0.049) and E17.5 (p = 0.022). Furthermore, the ability of Bmp-2 to induce Osx expression was significantly diminished in Fbln1-deficient mouse embryo fibroblasts. Together, these findings indicate that Fbln1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of Bmp signaling.

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