Linked Life Data

11274143

Source:http://linkedlifedata.com/resource/pubmed/id/11274143

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2001-6-4
pubmed:abstractText
The receptor activator of NF-kappaB (RANKL) is the essential signal required for full osteoclast (OC) development, activation, and survival. RANKL is highly expressed in areas of trabecular bone remodeling and inflammatory bone loss, is increased on marrow stromal cells or osteoblasts by osteotropic hormones or cytokines, and is neutralized by osteoprotegerin (OPG), a soluble decoy receptor also crucial for preventing arterial calcification. Vascular endothelial cells (VEC) are critically involved in bone development and remodeling and influence OC recruitment, formation, and activity. Although OCs develop and function in close association with bone VEC and sinusoids, signals mediating their interactions are not well known. Here, we show for the first time that human microvascular endothelial cells (HMVEC) express transcripts for both RANKL and OPG; inflammatory cytokines tumor necrosis factor-alpha and interleukin-1alpha elevate RANKL and OPG expression 5-40-fold in HMVEC (with an early OPG peak that declines as RANKL rises), and RANKL protein increases on the surface of tumor necrosis factor-alpha-activated HMVEC. Cytokine-activated HMVEC promoted the formation, fusion, and bone resorption of OCs formed in co-cultures with circulating human monocytic precursors via a RANKL-mediated mechanism fully antagonized by exogenous OPG. Furthermore, paraffin sections of human osteoporotic fractured bone exhibited increased RANKL immunostaining in vivo on VEC located near resorbing OCs in regions undergoing active bone turnover. Therefore, cytokine-activated VEC may contribute to inflammatory-mediated bone loss via regulated production of RANKL and OPG. VEC-derived OPG may also serve as an autocrine signal to inhibit blood vessel calcification.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20659-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11274143-Base Sequence, pubmed-meshheading:11274143-Bone Resorption, pubmed-meshheading:11274143-Cells, Cultured, pubmed-meshheading:11274143-Coculture Techniques, pubmed-meshheading:11274143-Cytokines, pubmed-meshheading:11274143-DNA Primers, pubmed-meshheading:11274143-Endothelium, Vascular, pubmed-meshheading:11274143-Gene Expression Regulation, pubmed-meshheading:11274143-Glycoproteins, pubmed-meshheading:11274143-Humans, pubmed-meshheading:11274143-Interleukin-1, pubmed-meshheading:11274143-Osteoclasts, pubmed-meshheading:11274143-Osteoprotegerin, pubmed-meshheading:11274143-RNA, Messenger, pubmed-meshheading:11274143-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:11274143-Receptors, Tumor Necrosis Factor, pubmed-meshheading:11274143-Tumor Necrosis Factor-alpha
pubmed:year
2001
pubmed:articleTitle
Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis.
pubmed:affiliation
Department of Biology, Washington University, St. Louis, Missouri 63130, USA. collin@biology.wustl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.