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Retinol-binding protein 4 downregulation during osteogenesis and its localization to non-endocytic vesicles in human cranial suture mesenchymal cells suggest a novel tissue function.
Histochem Cell Biol 2013; 139(1):75-87HC

Abstract

Craniosynostosis is a developmental disorder of the skull arising from premature bony fusion of cranial sutures, the sites of skull bone growth. In a recent gene microarray study, we demonstrated that retinol-binding protein 4 (RBP4) was the most highly downregulated gene in suture tissue during the pathological process of premature bony fusion. To gain insight into the function of RBP4 in cranial sutures, we analysed primary cells cultured from human cranial suture mesenchyme. These cells express RBP4 but not CRBP1, cellular retinol-binding protein 1, the typical cytoplasmic retinol storage protein. Using flow cytometry, we showed that suture mesenchymal cells express the RBP4 receptor, STRA6, on the cell surface. In a cell culture model of cranial osteogenesis, we found that RBP4 was significantly downregulated during mineralization, analogous to its decrease in pathological suture fusion. We found that cranial suture cells do not secrete detectable levels of RBP4, suggesting that it acts in a cell-autonomous manner. High-resolution confocal microscopy with a panel of antibody markers of cytoplasmic organelles demonstrated that RBP4 was present in several hundred cytoplasmic vesicles of about 300 nm in diameter which, in large part, were conspicuously distinct from the ER, the Golgi and endosomes of the endocytic pathway. We speculate that in suture mesenchymal cells, endogenous RBP4 receives retinol from STRA6 and the RBP4-retinol complex is stored in vesicles until needed for conversion to retinoic acid in the process of osteogenesis. This study extends the role of RBP4 beyond that of a serum transporter of retinol and implicates a broader role in osteogenesis.

Authors+Show Affiliations

Women's and Children's Health Research Institute, 72 King William Road, North Adelaide, SA 5006, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22878527

Citation

Leitch, Victoria D., et al. "Retinol-binding Protein 4 Downregulation During Osteogenesis and Its Localization to Non-endocytic Vesicles in Human Cranial Suture Mesenchymal Cells Suggest a Novel Tissue Function." Histochemistry and Cell Biology, vol. 139, no. 1, 2013, pp. 75-87.
Leitch VD, Dwivedi PP, Anderson PJ, et al. Retinol-binding protein 4 downregulation during osteogenesis and its localization to non-endocytic vesicles in human cranial suture mesenchymal cells suggest a novel tissue function. Histochem Cell Biol. 2013;139(1):75-87.
Leitch, V. D., Dwivedi, P. P., Anderson, P. J., & Powell, B. C. (2013). Retinol-binding protein 4 downregulation during osteogenesis and its localization to non-endocytic vesicles in human cranial suture mesenchymal cells suggest a novel tissue function. Histochemistry and Cell Biology, 139(1), pp. 75-87. doi:10.1007/s00418-012-1011-7.
Leitch VD, et al. Retinol-binding Protein 4 Downregulation During Osteogenesis and Its Localization to Non-endocytic Vesicles in Human Cranial Suture Mesenchymal Cells Suggest a Novel Tissue Function. Histochem Cell Biol. 2013;139(1):75-87. PubMed PMID: 22878527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retinol-binding protein 4 downregulation during osteogenesis and its localization to non-endocytic vesicles in human cranial suture mesenchymal cells suggest a novel tissue function. AU - Leitch,Victoria D, AU - Dwivedi,Prem P, AU - Anderson,Peter J, AU - Powell,Barry C, Y1 - 2012/08/10/ PY - 2012/07/28/accepted PY - 2012/8/11/entrez PY - 2012/8/11/pubmed PY - 2013/6/13/medline SP - 75 EP - 87 JF - Histochemistry and cell biology JO - Histochem. Cell Biol. VL - 139 IS - 1 N2 - Craniosynostosis is a developmental disorder of the skull arising from premature bony fusion of cranial sutures, the sites of skull bone growth. In a recent gene microarray study, we demonstrated that retinol-binding protein 4 (RBP4) was the most highly downregulated gene in suture tissue during the pathological process of premature bony fusion. To gain insight into the function of RBP4 in cranial sutures, we analysed primary cells cultured from human cranial suture mesenchyme. These cells express RBP4 but not CRBP1, cellular retinol-binding protein 1, the typical cytoplasmic retinol storage protein. Using flow cytometry, we showed that suture mesenchymal cells express the RBP4 receptor, STRA6, on the cell surface. In a cell culture model of cranial osteogenesis, we found that RBP4 was significantly downregulated during mineralization, analogous to its decrease in pathological suture fusion. We found that cranial suture cells do not secrete detectable levels of RBP4, suggesting that it acts in a cell-autonomous manner. High-resolution confocal microscopy with a panel of antibody markers of cytoplasmic organelles demonstrated that RBP4 was present in several hundred cytoplasmic vesicles of about 300 nm in diameter which, in large part, were conspicuously distinct from the ER, the Golgi and endosomes of the endocytic pathway. We speculate that in suture mesenchymal cells, endogenous RBP4 receives retinol from STRA6 and the RBP4-retinol complex is stored in vesicles until needed for conversion to retinoic acid in the process of osteogenesis. This study extends the role of RBP4 beyond that of a serum transporter of retinol and implicates a broader role in osteogenesis. SN - 1432-119X UR - https://www.unboundmedicine.com/medline/citation/22878527/Retinol_binding_protein_4_downregulation_during_osteogenesis_and_its_localization_to_non_endocytic_vesicles_in_human_cranial_suture_mesenchymal_cells_suggest_a_novel_tissue_function_ L2 - https://dx.doi.org/10.1007/s00418-012-1011-7 DB - PRIME DP - Unbound Medicine ER -