# BMP3 Deficiency Accelerates Cartilage-to-Bone Transition in Ectopic Bone

## TL;DR

This study shows that a lack of BMP3 in mice speeds up the formation of bone from cartilage in an unusual location, suggesting BMP3 normally controls this process.

## Contribution

The study reveals a novel role for BMP3 in regulating cartilage-to-bone transition through its effects on progenitor cell populations and gene expression.

## Key findings

- Bmp3-/- mice showed significantly more ectopic bone formation compared to wild-type mice after 14 days.
- Transcriptomic analysis revealed upregulation of hundreds of genes in Bmp3-/- mice, indicating altered cellular processes.
- BMP3 deficiency was associated with advanced cartilage-to-bone remodeling and altered bone marrow cell composition.

## Abstract

Background: Ectopic bone formation models provide useful insights into bone tissue formation and remodeling processes. The use of a subcutaneous site emphasizes the focus on cytokine signaling and cell migration and proliferation while minimizing the effect of mechanical loading and direct interaction with surrounding stem cells. Methods: To study the effect of BMP3 on bone formation and remodeling, Bmp3-/- mice were subcutaneously implanted with an autologous blood coagulum device containing BMP6, and bone formation was examined at days 7 and 14 post-implantation. Bone marrow cell composition was assessed using FACS. Formation of ectopic bone was analyzed using micro-CT, immunohistochemistry, and RNAseq to obtain transcriptomic data. Results: Bone marrow from Bmp3-/- mice showed reduced lymphoid-lineage subsets, expanded myeloid lineage, and altered proportions of several osteochondroprogenitor subsets. A limited amount of newly formed bone tissue was seen in the implants after 7 days, while ectopic bone was more evident after 14 days, with significantly more bone in the Bmp3-/- mice compared to WT mice. Localization of Sox9 and Runx2 showed a more advanced stage of bone tissue remodeling in Bmp3-/- mice. Transcriptomic analysis showed upregulation of approximately 1700 genes on day 7 and 190 genes on day 14. Conclusions: These results suggest that BMP3 regulates the composition of bone and cartilage progenitor populations in bone marrow and consequently bone formation by arresting the remodeling of cartilage to bone tissue. The lack of BMP3 in ectopic bone accelerates the transition from the cartilaginous template to proper bone tissue.