Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions.

Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Research Abstract Details 

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Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Abstract Text:

Christopher W Borysenko, ,Reed D Griswold,Yanan Li,Anand Krishnan V Iyer,Beatrice B Yaroslavskiy,Allison C Sharrow,Harry C Blair,

We previously reported that a soluble form of the TNF-family receptor death receptor-3 (DR3) is expressed in osteoblasts. DR3 regulates death or differentiation in other tissues, and DR3 ligands occur in bone, but the function of DR3 in the osteoblast was unknown. We studied the expression of DR3 and the effects crosslinking antibodies to DR3 or of natural DR3 ligands in human osteoblasts. Western analysis showed that nontransformed osteoblasts and the MG63 osteosarcoma cell line produce both soluble decoy receptor and transmembrane isoforms of DR3. Cell surface labeling showed that low and high DR3-expressing osteoblast populations occur. Verification of by cloning showed a point mutation in DR3 from MG63 cells. Activation of DR3 by antibody crosslinking or with DR3 ligands caused apoptosis in osteoblasts and in MG63 cells, but only in low-density cell cultures. In dense cultures apoptosis did not occur, but nuclear factor-kappaB nuclear translocation was observed under some conditions. Crosslinking of DR3 in high-density MG63 cultures blocked expression of bone matrix elements. DR3 activation in high-density nontransformed osteoblasts had only minor effects on cell maturation. We conclude that DR3 activation can mediate apoptosis in osteoblasts. Its activity is, however, highly restricted by its soluble ligand-binding isoform and possibly also by alternate survival signals. In the presence of survival signals, DR3 may affect cell maturation although effects on differentiation were clearly seen only in the MG63 transformed cell line.

Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Publishing Authors By Initials

CW Borysenko,V ,RD Griswold,Y Li,AK Iyer,BB Yaroslavskiy,AC Sharrow,HC Blair,

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Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of cellular physiology

VOLUME: 209

Page Numbers: 1021-8

Journal Abbreviation: J. Cell. Physiol.

ISSN: 0021-9541

DAY: 3

MONTH: Dec

YEAR: 2006

Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Information

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LANGUAGE: eng

NlmUniqueID: 50222

Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Keywords Mesh Terms:

KEYWORDS: Receptors, Tumor Necrosis Factor, Member

MESH TERMS: metabolism

Chemical & Substance for Abstract: Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions. Information

Substance Name: Receptors, Tumor Necrosis Factor, Member

Registry Number: 0

Grant and Affiliation Information for Death receptor-3 mediates apoptosis in human osteoblasts under narrowly regulated conditions.

AFFILIATION: Interdisciplinary Laboratory, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.

Country: United States

AGENCY: United States NIAMS

GRANT: AR 47700

ACRONYM: AR

MEDLINETA: J Cell Physiol

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