The role of cadherin in the generation of multinucleated osteoclasts from mononuclear precursors in murine marrow.
Open Access
- 1 June 1995
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 95 (6), 2757-2765
- https://doi.org/10.1172/jci117979
Abstract
A critical step in bone resorption is the fusion of mononuclear osteoclast precursors to form multinucleated osteoclasts. However, little is known of the molecular mechanisms that are responsible for this important process. Since the expression of proteins in the cadherin family of homophilic calcium-dependent cell adhesion molecules is involved in the fusion process for certain other cells, we examined their role in osteoclast formation. Immunohistochemical examination of human and mouse bone using monoclonal antibodies to human and mouse E-cadherin clearly demonstrated positive staining in osteoclasts. N- and P-cadherin were not detected. In cultures of murine marrow mononuclear cells in which osteoclasts form by cell fusion, E-cadherin expression determined by Western blotting reached the highest levels as fusion was taking place. Expression of E-cadherin gene fragment was also detected in the marrow cultures by polymerase chain reaction. To study the functional role of E-cadherin expression in osteoclastic differentiation, neutralizing monoclonal antibodies were examined for their effects on osteoclast formation. The antibodies decreased the number of tartrate-resistant acid phosphatase (a marker of murine osteoclast)-positive multinucleated cell (TRAP-positive MNC) by inhibiting the fusion of mononuclear osteoclast precursors, but not proliferation of these cells or their attachment to plastic dish surfaces. This inhibitory effect was reversible. Furthermore, synthetic peptides containing the cell adhesion recognition sequence of cadherins also decreased TRAP-positive MNC formation. The antibodies and peptides inhibited not only osteoclast formation but also bone resorption. Antibodies to other types of cadherins and control rat IgG had no effects in these culture systems. Our findings suggest that E-cadherin expression may be involved in fusion (differentiation) of hemopoietic osteoclast precursors into mature multinucleated osteoclasts.Keywords
This publication has 33 references indexed in Scilit:
- The structural and functional analysis of cadherin calcium-dependent cell adhesion moleculesCurrent Opinion in Cell Biology, 1993
- Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin geneNature, 1993
- Histomorphometric and immunocytochemical studies of src-related osteopetrosisBone, 1993
- Fibroblast growth factor receptors contain a conserved HAV region common to cadherins and influenza strain a hemagglutinins: A role in protein-protein interactions?Developmental Biology, 1992
- E-cadherin expression in a particular subset of sensory neuronsDevelopmental Biology, 1992
- Cadherin Cell Adhesion Receptors as a Morphogenetic RegulatorScience, 1991
- Identification of a cadherin cell adhesion recognition sequenceDevelopmental Biology, 1990
- Identification of a conserved region common to cadherins and influenza strain A hemagglutininsJournal of Molecular Biology, 1990
- Relationship between interleukin-1 and prostaglandins in resorbing neonatal calvariaJournal of Bone and Mineral Research, 1989
- Activation of the bone-derived latent TGF beta complex by isolated osteoclastsBiochemical and Biophysical Research Communications, 1989