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Retinoic acid enhances osteogenesis in cranial suture-derived mesenchymal cells: potential mechanisms of retinoid-induced craniosynostosis.
Plast Reconstr Surg 2010; 125(5):1352-61PR

Abstract

BACKGROUND

In utero retinoid exposure results in numerous craniofacial malformations, including craniosynostosis. Although many malformations associated with retinoic acid syndrome are associated with neural crest defects, the specific mechanisms of retinoid-induced craniosynostosis remain unclear. The authors used the culture of mouse cranial suture-derived mesenchymal cells to probe the potential cellular mechanisms of this teratogen to better elucidate mechanisms of retinoid-induced suture fusion.

METHODS

Genes associated with retinoid signaling were assayed in fusing (posterofrontal) and patent (sagittal, coronal) sutures by quantitative real-time polymerase chain reaction. Cultures of mouse suture-derived mesenchymal cells from the posterofrontal suture were established from 4-day-old mice. Cells were cultured with all-trans retinoic acid (1 and 5 muM). Proliferation, osteogenic differentiation, and specific gene expression were assessed.

RESULTS

Mouse sutures were found to express genes necessary for retinoic acid synthesis, binding, and signal transduction, demonstrated by quantitative real-time polymerase chain reaction (Raldh1, Raldh2, Raldh3, and Rbp4). These genes were not found to be differentially expressed in fusing as compared with patent cranial sutures in vivo. Addition of retinoic acid enhanced the osteogenic differentiation of suture-derived mesenchymal cells in vitro, including up-regulation of alkaline phosphatase activity and Runx2 expression. Contemporaneously, cellular proliferation was repressed, as shown by proliferative cell nuclear antigen expression. The pro-osteogenic effect of retinoic acid was accompanied by increased gene expression of several hedgehog and bone morphogenetic protein ligands.

CONCLUSIONS

Retinoic acid represses proliferation and enhances osteogenic differentiation of suture-derived mesenchymal cells. These in vitro data suggest that retinoid exposure may lead to premature cranial suture fusion by means of enhanced osteogenesis and hedgehog and bone morphogenetic protein signaling.

Authors+Show Affiliations

Hagey Pediatric Regenerative Research Laboratory, Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20134361

Citation

James, Aaron W., et al. "Retinoic Acid Enhances Osteogenesis in Cranial Suture-derived Mesenchymal Cells: Potential Mechanisms of Retinoid-induced Craniosynostosis." Plastic and Reconstructive Surgery, vol. 125, no. 5, 2010, pp. 1352-61.
James AW, Levi B, Xu Y, et al. Retinoic acid enhances osteogenesis in cranial suture-derived mesenchymal cells: potential mechanisms of retinoid-induced craniosynostosis. Plast Reconstr Surg. 2010;125(5):1352-61.
James, A. W., Levi, B., Xu, Y., Carre, A. L., & Longaker, M. T. (2010). Retinoic acid enhances osteogenesis in cranial suture-derived mesenchymal cells: potential mechanisms of retinoid-induced craniosynostosis. Plastic and Reconstructive Surgery, 125(5), pp. 1352-61. doi:10.1097/PRS.0b013e3181d62980.
James AW, et al. Retinoic Acid Enhances Osteogenesis in Cranial Suture-derived Mesenchymal Cells: Potential Mechanisms of Retinoid-induced Craniosynostosis. Plast Reconstr Surg. 2010;125(5):1352-61. PubMed PMID: 20134361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinoic acid enhances osteogenesis in cranial suture-derived mesenchymal cells: potential mechanisms of retinoid-induced craniosynostosis. AU - James,Aaron W, AU - Levi,Benjamin, AU - Xu,Yue, AU - Carre,Antoine L, AU - Longaker,Michael T, PY - 2010/2/6/entrez PY - 2010/2/6/pubmed PY - 2010/5/26/medline SP - 1352 EP - 61 JF - Plastic and reconstructive surgery JO - Plast. Reconstr. Surg. VL - 125 IS - 5 N2 - BACKGROUND: In utero retinoid exposure results in numerous craniofacial malformations, including craniosynostosis. Although many malformations associated with retinoic acid syndrome are associated with neural crest defects, the specific mechanisms of retinoid-induced craniosynostosis remain unclear. The authors used the culture of mouse cranial suture-derived mesenchymal cells to probe the potential cellular mechanisms of this teratogen to better elucidate mechanisms of retinoid-induced suture fusion. METHODS: Genes associated with retinoid signaling were assayed in fusing (posterofrontal) and patent (sagittal, coronal) sutures by quantitative real-time polymerase chain reaction. Cultures of mouse suture-derived mesenchymal cells from the posterofrontal suture were established from 4-day-old mice. Cells were cultured with all-trans retinoic acid (1 and 5 muM). Proliferation, osteogenic differentiation, and specific gene expression were assessed. RESULTS: Mouse sutures were found to express genes necessary for retinoic acid synthesis, binding, and signal transduction, demonstrated by quantitative real-time polymerase chain reaction (Raldh1, Raldh2, Raldh3, and Rbp4). These genes were not found to be differentially expressed in fusing as compared with patent cranial sutures in vivo. Addition of retinoic acid enhanced the osteogenic differentiation of suture-derived mesenchymal cells in vitro, including up-regulation of alkaline phosphatase activity and Runx2 expression. Contemporaneously, cellular proliferation was repressed, as shown by proliferative cell nuclear antigen expression. The pro-osteogenic effect of retinoic acid was accompanied by increased gene expression of several hedgehog and bone morphogenetic protein ligands. CONCLUSIONS: Retinoic acid represses proliferation and enhances osteogenic differentiation of suture-derived mesenchymal cells. These in vitro data suggest that retinoid exposure may lead to premature cranial suture fusion by means of enhanced osteogenesis and hedgehog and bone morphogenetic protein signaling. SN - 1529-4242 UR - https://www.unboundmedicine.com/medline/citation/20134361/Retinoic_acid_enhances_osteogenesis_in_cranial_suture_derived_mesenchymal_cells:_potential_mechanisms_of_retinoid_induced_craniosynostosis_ L2 - http://Insights.ovid.com/pubmed?pmid=20134361 DB - PRIME DP - Unbound Medicine ER -