(P 255) TRUNCATED FOS REDUCES OSTEOGENIC DIFFERENTIATION CAPACITY IN OSTEOID OSTEOMA AND OSTEOBLASTOMA

Objective: To investigate how alterations in FOS affect osteogenic differentiation and proliferation in osteoid osteoma and osteoblastoma.

Methods: Using an in vitro model, fetal mesenchymal stem cells were transduced to overexpress truncated (FOSΔ), FOS with a deletion (FOSΔ376-377) or mutation (FOSL376N) in the C-terminal domain, full-length FOS and were compared to wild-type mesenchymal stem cells. Osteogenic differentiation was assessed by measuring mineralization, ALP expression and ALP activity and the proliferating rate by Presto Blue staining and nuclei count. After one, two and three weeks of osteogenic differentiation, RNA was isolated for transcriptome analysis.

Results: Osteogenic differentiation and proliferation rate were reduced in cells overexpressing truncated FOS (FOSΔ), or FOS with a deletion (FOSΔ376-377) or mutation (FOSL376N) in the C-terminal domain, compared to wild-type mesenchymal stem cells. In contrast, cells overexpressing full-length FOS showed increased proliferation and almost completely lost mineralization. Transcriptome analysis is currently ongoing.

Conclusion: These results demonstrate that the balance between differentiation and proliferation can be disrupted by changes in FOS expression, which may explain the indolent growth and formation of woven bone observed in osteoid osteoma and osteoblastoma.