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Pagetic osteoclasts formed in vitro: absence of paracrystalline inclusions
G D Roodman1, Y Ohsaki, M M Miller
1Department of Medicine, University of Texas Health Science Center, San Antonio, USA.
Abstract:
In Paget's disease of bone, osteoclasts are increased in number and size and contain intracellular paramyxoviral-like inclusions which cross-react with antibody against measles, respiratory syncytial, and canine distemper viral nucleocapsid antigens. Moreover, measles virus nucleocapsid transcripts are present in pagetic osteoclasts and their mononuclear precursors formed in vitro. The present study was undertaken to morphologically assess pagetic osteoclasts formed in culture; special attention has been directed towards the ultrastructural identification of nuclear and cytoplasmic inclusions. Pagetic osteoclasts were produced in long-term cultures of non-adherent bone marrow mononuclear cells derived from involved bone of patients with Paget's disease. These cultured osteoclasts had many of the ultrastructural features of pagetic osteoclasts in vivo. Of interest, no viral-like inclusions were observed in either the multinucleated osteoclasts or mononuclear cell precursors in these cultures. These data suggest that other factors in the bone microenvironment are required for viral nucleocapsid formation in pagetic osteoclasts.
Insights
Paget
Area of Science:
- Bone biology
- Virology
- Cellular pathology
Background:
- Paget's disease of bone features enlarged osteoclasts with paramyxoviral inclusions.
- Measles virus nucleocapsid transcripts are detected in pagetic osteoclasts.
- The role of viral infections in Paget's disease pathogenesis remains under investigation.
Purpose of the Study:
- To morphologically assess cultured pagetic osteoclasts.
- To investigate the ultrastructural presence of nuclear and cytoplasmic inclusions in these cells.
- To determine if cultured osteoclasts recapitulate in vivo viral findings.
Main Methods:
- Pagetic osteoclasts were generated in long-term cultures from bone marrow mononuclear cells of patients with Paget's disease.
- Ultrastructural analysis was performed on cultured multinucleated osteoclasts and mononuclear precursors.
- Cells were derived from bone tissue affected by Paget's disease.
Main Results:
- Cultured pagetic osteoclasts exhibited ultrastructural characteristics similar to those observed in vivo.
- No viral-like inclusions were identified in either multinucleated osteoclasts or mononuclear cell precursors in culture.
- The study successfully cultured osteoclasts with features of Paget's disease.
Conclusions:
- The absence of viral inclusions in cultured osteoclasts suggests a dependence on the bone microenvironment.
- Factors within the bone microenvironment may be necessary for paramyxoviral nucleocapsid formation in Paget's disease.
- Further research is needed to elucidate the specific environmental factors involved.