Fig. 1.

Osteogenic differentiation during intramembranous ossification. 1- MSCs migrate to the site of bone formation and proliferate. 2- MSCs then differentiate into osteoprogenitors and preosteoblasts. 3- These two cell lines deposit the unmineralized bone matrix known as osteoid matrix and differentiate into mature osteoblasts. Osteoid matrix is mineralized by deposition of Ca²⁺. 4- Some osteoblasts are trapped in the mineralized matrix, which later become osteocytes. Expression of the skeletal transcription factors Runx2 and Osterix occurs throughout this process. Also, activation of canonical and non-canonical Wnt signaling as well as BMP/Smad signaling are necessary for various aspects including differentiation, migration and proliferation during intramembranous ossification [11]. Upregulation of the mentioned osteogenic proteins and signaling pathways in the laboratory is often the mechanism through which many small molecules induce osteogenic differentiation of stem cells