Abstract：
:Fibrodysplasia ossificans progressiva is a disabling genetic disorder characterized by congenital skeletal malformations and progressive heterotopic ossification. New episodes of ossification are heralded by preosseous inflammatory lesions replete with B and T lymphocytes that overexpress bone morphogenetic protein-4. NF-kappaB is an inflammatory mediator that plays a critical role in developmental skeletogenesis and in suppression of bone morphogenetic protein-4 expression. Because of its multiple roles in inflammation, skeletogenesis, and bone morphogenetic protein-4 regulation, NF-kappaB may play an important functional role in the pathogenesis of fibrodysplasia ossificans progressiva. To clarify the potential role of NF-kappaB in the pathophysiologic features of fibrodysplasia ossificans progressiva, the role of NF-kappaB in regulating bone morphogenetic protein-4 signaling in patient-derived lymphoblastoid cell lines was examined. General NF-kappaB activity and specific NF-kappaB suppression of bone morphogenetic protein-4 expression were not altered in fibrodysplasia ossificans progressiva. In addition, despite the proximity of the gene for the p50 subunit of NF-kappaB (NFKB1 on long arm of chromosome 4) to the recently mapped locus for fibrodysplasia ossificans progressiva, a detailed linkage exclusion analysis in four multigenerational families with the disorder excluded NFKB1 as the causative gene for fibrodysplasia ossificans progressiva. These data exonerate NF-kappaB as the critical molecular and genetic pathogenic mediator in fibrodysplasia ossificans progressiva and, therefore, implicate a defect in another regulatory pathway as the cause for bone morphogenetic protein-4 overexpression in the disease.
journal_name
Clin Orthop Relat Resjournal_title
Clinical orthopaedics and related researchauthors
Ahn J,Feldman G,Terry L,Shore EM,Kaplan FSdoi
10.1097/01.blo.0000030075.92399.11subject
Has Abstractpub_date
2003-01-01 00:00:00pages
205-13issue
406eissn
0009-921Xissn
1528-1132pub_type
杂志文章abstract：:The osteopenia associated with advanced age appears to be a universal phenomenon in humans and animals, but the mechanisms by which it occurs are understood incompletely. However, the explanation must lie in an absolute or relative diminution in the level of osteoblastic bone-forming activity when compared with osteoc...
journal_title：Clinical orthopaedics and related research
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journal_title：Clinical orthopaedics and related research
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1976-10-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章,评审
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更新日期：1990-10-01 00:00:00
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journal_title：Clinical orthopaedics and related research
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更新日期：1986-04-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
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更新日期：1993-05-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1984-06-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：10.1097/00003086-200111000-00049
更新日期：2001-11-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1992-12-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1975-10-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1985-12-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：10.1097/00003086-200004000-00026
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：10.1097/01.blo.0000238779.12069.e1
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
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journal_title：Clinical orthopaedics and related research
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章,评审
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更新日期：2004-10-01 00:00:00
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journal_title：Clinical orthopaedics and related research
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
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journal_title：Clinical orthopaedics and related research
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更新日期：2011-03-01 00:00:00
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journal_title：Clinical orthopaedics and related research
pub_type： 杂志文章,评审
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更新日期：2006-11-01 00:00:00
