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Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures.
J Bone Miner Res 2003; 18(4):751-9JB

Abstract

Craniosynostosis, the premature fusion of the skull bones at the sutures, represents a disruption to the coordinated growth and development of the expanding brain and calvarial vault and is the second most common birth defect that affects the craniofacial complex. Mutations in the human homeobox-containing gene, Msx2, have been shown to cause Boston type craniosynostosis, and we have shown that overexpression of Msx2 leads to craniosynostosis in mice. Activating mutations in fibroblast growth factor (FGF) receptors are thought to cause craniosynostosis in Crouzon, Apert, Jackson-Weiss, Beare-Stevenson, and Muenke syndromes. To mimic activated signaling by mutated FGF receptors, we used heparin acrylic beads to deliver FGF ligands to mouse calvaria and demonstrated increased Msx2, Runx2, Bsp, and Osteocalcin gene expression, decreased cell proliferation, and suture obliteration and fusion. FGF2 elicited the greatest increase in Msx2 expression, and FGF1 was most likely to cause suture obliteration and fusion. Of the three sutures studied, the coronal suture exhibited the greatest increase in Msx2 expression and was the most likely to undergo obliteration and fusion. These results are intriguing because the coronal suture is the most commonly affected suture in syndromic craniosynostosis. These results suggest that Msx2 is a downstream target of FGF receptor signaling and that increased FGF signaling leads to osteogenic differentiation by sutural mesenchyme in mouse calvaria. These results are consistent with the hypotheses that increased Msx2 expression and activated signaling by mutated FGF receptors lead to craniosynostosis.

Authors+Show Affiliations

Department of Orthodontics and Pediatric Dentistry, The University of Michigan School of Dentistry, Ann Arbor, Michigan 48109-1078, USA. ignelzi@umich.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12674336

Citation

Ignelzi, Michael A., et al. "Fibroblast Growth Factors Lead to Increased Msx2 Expression and Fusion in Calvarial Sutures." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 18, no. 4, 2003, pp. 751-9.
Ignelzi MA, Wang W, Young AT. Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. J Bone Miner Res. 2003;18(4):751-9.
Ignelzi, M. A., Wang, W., & Young, A. T. (2003). Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 18(4), pp. 751-9.
Ignelzi MA, Wang W, Young AT. Fibroblast Growth Factors Lead to Increased Msx2 Expression and Fusion in Calvarial Sutures. J Bone Miner Res. 2003;18(4):751-9. PubMed PMID: 12674336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factors lead to increased Msx2 expression and fusion in calvarial sutures. AU - Ignelzi,Michael A,Jr AU - Wang,Wei, AU - Young,Andrew T, PY - 2003/4/4/pubmed PY - 2003/12/5/medline PY - 2003/4/4/entrez SP - 751 EP - 9 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 18 IS - 4 N2 - Craniosynostosis, the premature fusion of the skull bones at the sutures, represents a disruption to the coordinated growth and development of the expanding brain and calvarial vault and is the second most common birth defect that affects the craniofacial complex. Mutations in the human homeobox-containing gene, Msx2, have been shown to cause Boston type craniosynostosis, and we have shown that overexpression of Msx2 leads to craniosynostosis in mice. Activating mutations in fibroblast growth factor (FGF) receptors are thought to cause craniosynostosis in Crouzon, Apert, Jackson-Weiss, Beare-Stevenson, and Muenke syndromes. To mimic activated signaling by mutated FGF receptors, we used heparin acrylic beads to deliver FGF ligands to mouse calvaria and demonstrated increased Msx2, Runx2, Bsp, and Osteocalcin gene expression, decreased cell proliferation, and suture obliteration and fusion. FGF2 elicited the greatest increase in Msx2 expression, and FGF1 was most likely to cause suture obliteration and fusion. Of the three sutures studied, the coronal suture exhibited the greatest increase in Msx2 expression and was the most likely to undergo obliteration and fusion. These results are intriguing because the coronal suture is the most commonly affected suture in syndromic craniosynostosis. These results suggest that Msx2 is a downstream target of FGF receptor signaling and that increased FGF signaling leads to osteogenic differentiation by sutural mesenchyme in mouse calvaria. These results are consistent with the hypotheses that increased Msx2 expression and activated signaling by mutated FGF receptors lead to craniosynostosis. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/12674336/Fibroblast_growth_factors_lead_to_increased_Msx2_expression_and_fusion_in_calvarial_sutures_ L2 - https://doi.org/10.1359/jbmr.2003.18.4.751 DB - PRIME DP - Unbound Medicine ER -