Tags

Type your tag names separated by a space and hit enter

Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva.
N Engl J Med. 1996 Aug 22; 335(8):555-61.NEJM

Abstract

BACKGROUND

Fibrodysplasia ossificans progressiva is a heritable disorder of connective tissue characterized by congenital malformation of the great toes and postnatal formation of ectopic bone. Although the disorder was first described more than 300 years ago, the genetic defect and pathophysiology remain unknown. Bone morphogenetic proteins are potent bone-inducing morphogens that participate in the developmental organization of the skeleton, and increased production of one or more of these proteins has been proposed as the cause of fibrodysplasia ossificans progressiva.

METHODS

We studied lymphoblastoid cell lines established from peripheral-blood mononuclear cells of patients with fibrodysplasia ossificans progressiva and fibroblast-like cell lines derived from lesional and nonlesional tissue. We used Northern blot analysis and ribonuclease protection assays to measure the expression of messenger RNA (mRNA) of bone morphogenetic proteins 1 to 7 and immunohistochemical analysis to examine protein expression.

RESULTS

Among the bone morphogenetic proteins and mRNAs examined, only bone morphogenetic protein 4 and its mRNA were present in increased levels in cells derived from an early fibroproliferative lesion in a patient with fibrodysplasia ossificans progressiva. Bone morphogenetic protein 4 mRNA was expressed in lymphoblastoid cell lines from 26 of 32 patients with fibrodysplasia ossificans progressiva but from only 1 of 12 normal subjects (P<0.001). Bone morphogenetic protein 4 and its mRNA were detected in the lymphoblastoid cell lines from a man with fibrodysplasia ossificans progressiva and his three affected children (two girls and a boy), but not from the children's unaffected mother. No other bone morphogenetic proteins were detected.

CONCLUSIONS

Overexpression of a potent bone-inducing morphogen (bone morphogenetic protein 4) in lymphocytes is associated with the disabling ectopic osteogenesis of fibrodysplasia ossificans progressiva.

Authors+Show Affiliations

Department of Orthopaedic Surgery, University of Pennsylvania School ofMedicine, Philadelphia 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, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8678932

Citation

Shafritz, A B., et al. "Overexpression of an Osteogenic Morphogen in Fibrodysplasia Ossificans Progressiva." The New England Journal of Medicine, vol. 335, no. 8, 1996, pp. 555-61.
Shafritz AB, Shore EM, Gannon FH, et al. Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med. 1996;335(8):555-61.
Shafritz, A. B., Shore, E. M., Gannon, F. H., Zasloff, M. A., Taub, R., Muenke, M., & Kaplan, F. S. (1996). Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. The New England Journal of Medicine, 335(8), 555-61.
Shafritz AB, et al. Overexpression of an Osteogenic Morphogen in Fibrodysplasia Ossificans Progressiva. N Engl J Med. 1996 Aug 22;335(8):555-61. PubMed PMID: 8678932.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. AU - Shafritz,A B, AU - Shore,E M, AU - Gannon,F H, AU - Zasloff,M A, AU - Taub,R, AU - Muenke,M, AU - Kaplan,F S, PY - 1996/8/22/pubmed PY - 1996/8/22/medline PY - 1996/8/22/entrez SP - 555 EP - 61 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 335 IS - 8 N2 - BACKGROUND: Fibrodysplasia ossificans progressiva is a heritable disorder of connective tissue characterized by congenital malformation of the great toes and postnatal formation of ectopic bone. Although the disorder was first described more than 300 years ago, the genetic defect and pathophysiology remain unknown. Bone morphogenetic proteins are potent bone-inducing morphogens that participate in the developmental organization of the skeleton, and increased production of one or more of these proteins has been proposed as the cause of fibrodysplasia ossificans progressiva. METHODS: We studied lymphoblastoid cell lines established from peripheral-blood mononuclear cells of patients with fibrodysplasia ossificans progressiva and fibroblast-like cell lines derived from lesional and nonlesional tissue. We used Northern blot analysis and ribonuclease protection assays to measure the expression of messenger RNA (mRNA) of bone morphogenetic proteins 1 to 7 and immunohistochemical analysis to examine protein expression. RESULTS: Among the bone morphogenetic proteins and mRNAs examined, only bone morphogenetic protein 4 and its mRNA were present in increased levels in cells derived from an early fibroproliferative lesion in a patient with fibrodysplasia ossificans progressiva. Bone morphogenetic protein 4 mRNA was expressed in lymphoblastoid cell lines from 26 of 32 patients with fibrodysplasia ossificans progressiva but from only 1 of 12 normal subjects (P<0.001). Bone morphogenetic protein 4 and its mRNA were detected in the lymphoblastoid cell lines from a man with fibrodysplasia ossificans progressiva and his three affected children (two girls and a boy), but not from the children's unaffected mother. No other bone morphogenetic proteins were detected. CONCLUSIONS: Overexpression of a potent bone-inducing morphogen (bone morphogenetic protein 4) in lymphocytes is associated with the disabling ectopic osteogenesis of fibrodysplasia ossificans progressiva. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/8678932/Overexpression_of_an_osteogenic_morphogen_in_fibrodysplasia_ossificans_progressiva_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199608223350804?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -