# In vitro characterization of osteoblasts from craniofacial fibrous dysplasia of bone and their impact on bone homeostasis

## TL;DR

This study examines how bone cells from craniofacial fibrous dysplasia behave in the lab, revealing differences in bone formation and breakdown compared to other bone regions.

## Contribution

The study provides the first in vitro characterization of craniofacial fibrous dysplasia osteoblasts and their impact on bone homeostasis.

## Key findings

- Craniofacial FD osteoblasts show increased proliferation but reduced differentiation and mineralization.
- FD osteoblasts exhibit decreased osteoclastogenic potential due to impaired osteoclast formation.
- Shared and distinct features between craniofacial and appendicular FD osteoblasts were identified.

## Abstract

Fibrous Dysplasia (FD) is a benign and rare genetic disease characterized by progressive replacement of normal bone by a non-mineralized matrix. FD is caused by GNAS mutations that increase intracellular cAMP levels. While appendicular lesions have been extensively studied to enhance understanding and management of the disease, the pathogenesis of craniofacial lesions remains poorly described despite the embryological, phenotypic and mechanical differences between these two skeletal regions. Our objective was to evaluate the impact of craniofacial FD on bone homeostasis. Typical histological features, suh as “alphabet soup” appearance, were observed in craniofacial FD lesions. Higher intracellular cAMP levels were also noted in FD cultures derived from craniofacial lesions. We demonstrated an increased proliferative capacity in craniofacial FD osteoblasts, associated with decreased osteoblastic differentiation and a lack in mineralization abilities. Interestingly, we highlighted a decreased osteoclastogenic potential due to impaired osteoclast formation in FD-conditioned medium cultures, indicating a diminished osteoclastogenic potential of craniofacial FD osteoblasts. Our data suggest shared characteristics between osteoblasts from the craniofacial and the appendicular skeletons but also discrepancies regarding osteoclastic potential. Exploring these features could help explain the differences observed between appendicular and cranio-facial lesions and should lead to further studies on the pathogenesis of craniofacial fibrous dysplasia.

The online version contains supplementary material available at 10.1186/s13023-026-04262-0.