Linked Life Data

17948903

Source:http://linkedlifedata.com/resource/pubmed/id/17948903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-4-2
pubmed:abstractText
The death of osteocytes, the terminally differentiated cells of the osteoblast lineage that are embedded in bone and regulate remodeling, is significant to both normal and pathological bone resorption. Apoptotic osteocytes putatively release a clarion signal that enhances the development of the bone-resorbing osteoclasts and targets their migration to the breach in the osteocyte network. This phenomenon is thought to underlie normal repair of bone microdamage and contribute to the etiologies of inflammatory bone loss. The chromatin protein high mobility group box 1 protein (HMGB1) has been identified as an "alarmin" in other tissues. An alarmin is an endogenous molecule released by dead and dying cells that alert the innate immune system to damage and the need for tissue repair. Wang and colleagues presented evidence in a landmark 1999 study showing that released HMGB1 is a lethal mediator of sepsis. Extracellular HMGB1 is a ligand for the toll-like receptors (TLRs) and for the receptor for advanced glycation end products (RAGE) all of which amplify inflammation. Recent studies by our lab and others have shown that HMGB1 is a bone-active cytokine. It is released by apoptotic osteoblasts in vitro, including the MLO-Y4 osteocyte-like cells. Extracellular HMGB1 enhances the expression of RANKL, TNFalpha, and IL6 in osteoblastogenic bone marrow stromal cell cultures, and it is chemotactic to osteoclasts. In this prospectus we will review HMGB1 activity at the immune-bone interface and propose a role for HMGB1 as an osteocyte alarmin and mediator of normal remodeling and inflammatory bone loss.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-4644
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1671-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Is HMGB1 an osteocyte alarmin?
pubmed:affiliation
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. jbidwell@iupui.edu
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural