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HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells.
J Cell Biochem. 2007 Dec 15; 102(6):1493-503.JC

Abstract

Cell surface heparan sulfate proteoglycans (HSPGs) play important roles in morphogen gradient formation and cell signaling. Bone morphogenetic protein (BMP) signaling is dysregulated in fibrodysplasia ossificans progressiva (FOP), a disabling disorder of progressive heterotopic bone formation. Here, we investigated the role of HSPG glycosaminoglycan (GAG) side chains on BMP signaling and found increased total and HSPG-specific GAG chain levels and dysregulation in HSPG modulation of BMP signaling in FOP lymphoblastoid cells (LCLs). Specifically, HSPG profiling demonstrated abundant mRNA and protein levels of glypican 1 and syndecan 4 on control and FOP LCLs, with elevated core protein levels on FOP cells. Targeted downregulation of glypican 1 core protein synthesis by siRNA enhanced BMP signaling in control and FOP cells, while reduction of syndecan 4-core protein synthesis decreased BMP signaling in control, but not FOP cells. These results suggest that FOP cells are resistant to the stimulatory effects of cell surface HSPG GAG chains, but are susceptible to the inhibitory effects, as shown by downregulation of glypican 1. These data support that HSPG modulation of BMP signaling is altered in cells from patients with FOP and that altered HSPG-related BMP signaling may play a role in the pathogenesis of the disease.

Authors+Show Affiliations

Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA.No affiliation info availableNo affiliation info availableNo 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

17516498

Citation

O'Connell, Michael P., et al. "HSPG Modulation of BMP Signaling in Fibrodysplasia Ossificans Progressiva Cells." Journal of Cellular Biochemistry, vol. 102, no. 6, 2007, pp. 1493-503.
O'Connell MP, Billings PC, Fiori JL, et al. HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells. J Cell Biochem. 2007;102(6):1493-503.
O'Connell, M. P., Billings, P. C., Fiori, J. L., Deirmengian, G., Roach, H. I., Shore, E. M., & Kaplan, F. S. (2007). HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells. Journal of Cellular Biochemistry, 102(6), 1493-503.
O'Connell MP, et al. HSPG Modulation of BMP Signaling in Fibrodysplasia Ossificans Progressiva Cells. J Cell Biochem. 2007 Dec 15;102(6):1493-503. PubMed PMID: 17516498.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells. AU - O'Connell,Michael P, AU - Billings,Paul C, AU - Fiori,Jennifer L, AU - Deirmengian,Gregory, AU - Roach,Helmtrud I, AU - Shore,Eileen M, AU - Kaplan,Frederick S, PY - 2007/5/23/pubmed PY - 2008/3/14/medline PY - 2007/5/23/entrez SP - 1493 EP - 503 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 102 IS - 6 N2 - Cell surface heparan sulfate proteoglycans (HSPGs) play important roles in morphogen gradient formation and cell signaling. Bone morphogenetic protein (BMP) signaling is dysregulated in fibrodysplasia ossificans progressiva (FOP), a disabling disorder of progressive heterotopic bone formation. Here, we investigated the role of HSPG glycosaminoglycan (GAG) side chains on BMP signaling and found increased total and HSPG-specific GAG chain levels and dysregulation in HSPG modulation of BMP signaling in FOP lymphoblastoid cells (LCLs). Specifically, HSPG profiling demonstrated abundant mRNA and protein levels of glypican 1 and syndecan 4 on control and FOP LCLs, with elevated core protein levels on FOP cells. Targeted downregulation of glypican 1 core protein synthesis by siRNA enhanced BMP signaling in control and FOP cells, while reduction of syndecan 4-core protein synthesis decreased BMP signaling in control, but not FOP cells. These results suggest that FOP cells are resistant to the stimulatory effects of cell surface HSPG GAG chains, but are susceptible to the inhibitory effects, as shown by downregulation of glypican 1. These data support that HSPG modulation of BMP signaling is altered in cells from patients with FOP and that altered HSPG-related BMP signaling may play a role in the pathogenesis of the disease. SN - 0730-2312 UR - https://www.unboundmedicine.com/medline/citation/17516498/HSPG_modulation_of_BMP_signaling_in_fibrodysplasia_ossificans_progressiva_cells_ L2 - https://doi.org/10.1002/jcb.21370 DB - PRIME DP - Unbound Medicine ER -