Bone tissue is a specialized connective tissue, characterized by a mineralized extracellular matrix and an organized structure. It is constantly being remodeled through the coordinated actions of osteoblasts and osteoclasts. The canonical Wnt signaling pathway plays a central role in osteoblast differentiation. Genetic alterations in this pathway cause bone diseases such as sclerosing bone dysplasia, which are characterized by high bone mass caused by mutations in different genes. Patients with specific variants develop progressive osteocondensation of the cortical long bons and craniofacial bones, causing dysmorphia, nerve palsy headaches and deafness among other symptoms.

There is currently no treatment for these conditions. This study aims to evaluate the therapeutic potential of a molecule X in the treatment of these bone diseases. To this end, we created iPS models from three different patients (with different mutations). Mesenchymal stem cells (MSCs) were then derived from the iPS cells to perform differentiations into osteoblasts and chondrocytes in the presence of this molecule X.

After 2 to 3 weeks of differentiation, the cells were fixed for characterization. Alizarin Red S staining showed decreased mineralization in osteoblasts, while Alcian Blue staining indicated increased chondrocytes calcification. It therefore suggests that the molecule X impacts both osteoblasts and chondrocytes differentiation, and could thus improve patient outcomes.

To validate these findings, transcriptomic analyses and further assessment of the molecule X’s toxicity are required.