Tyler Y. Shimabukuro,1,2 James Pruneski,1 Courtney Lavin,3 Erica Y. Kao,4 Ashley Aratani,5 Sean P. Kelly1
1 Tripler Army Medical Center, Honolulu, HI
2 John A. Burns School of Medicine, University of Hawaiʻi, Honolulu, HI
3 Madigan Army Medical Center Orthopaedic Surgery, WA
4 Brooke Army Medical Center, San Antonio, TX
5 Department of Orthopedic Surgery, Pali Momi Medical Center, Aiea, HI
Introduction: Osteomorphs are newly identified cells formed by osteoclast fission. Unlike the previously accepted view that osteoclasts undergo apoptosis, osteomorphs can circulate and later fuse back into osteoclasts, suggesting a recycling process. This raises the possibility that dysregulated fission/fusion may contribute to tumorigenesis in bone tumors.
Methods: We analyzed single-cell RNA-seq data from 14 bone tumor samples (2 GCTB, 5 OS, 3 EWS, 4 CS) from the Gene Expression Omnibus. Osteomorphs were identified based on expression of BPGM, FBXO7, AXL, CD74, LEPROT, and CCR3. UMAP and Seurat v5 were used for dimensionality reduction and visualization.
Results: Osteomorphs were detected in 1/2 GCTB and 4/5 OS samples, averaging 5.1% of total cells (range: 4.8%–23%). Osteoclasts averaged 12%, with a mean osteomorph-to-osteoclast ratio of 0.75. Neither osteomorphs nor osteoclasts were detected in CS or EWS (threshold: 2.5%).
Conclusion: Osteomorphs are present in certain tumors like GCTB and OS but absent in CS and EWS. Their presence may reflect a novel mechanism in bone tumor biology and warrants further investigation.
