Regulation of the osteoblastic and chondrocytic differentiation of stem cells by the extracellular matrix and subsequent bone formation modes

While various factors have been reported to direct stem cell differentiation lineage, little is known about how nature orchestrates the mesenchymal stem cell (MSC) differentiation and bone morphogenesis during skeleton development and bone regeneration. The present study reports that the matrix has a critical regulating effect on MSC differentiation and the subsequent bone formation modes. A simply combined hydroxyapatite (HA)-collagen matrix stimulates the MSC differentiation into the osteoblastic lineage and leads to a straightforward intramembranous bone formation mode, in contrast to the chondrocytic differentiation and endochondral mode observed on HA-synthetic hydrogel matrix. The accelerated MSC condensation and robust MSC-matrix and MSC-MSC interactions on collagen-based matrix might be the critical factors contributing to such events, likely through the orchestrated signal cascades and cellular events modulated by the extracellular matrix. The results demonstrate that matrix plays critical role in modulating the stem cell differentiation lineage and bone formation mode, which has been largely overlooked.