New discovery of chondrocytes in fracture healing: A review of chondrocyte journey

Previous studies have confirmed that chondrocytes are derived from mesenchymal stem cells (MSCs) and mature into hypertrophic chondrocytes during endochondral ossification. This maturation is followed by apoptosis, which induces vascular invasion, cartilage matrix degradation, and osteoblast differentiation. In addition to this classical transdifferentiation pathway, recent studies have shown that chondrocytes can also be derived from periosteal stem cells (PSCs). Using lineage-tracing techniques to detect the transdifferentiated forms of chondrocytes during endochondral ossification, several new models of transdifferentiation have been discovered, such as a chondrocyte-to-osteoblast precursor transdifferentiation model, a chondrocyte dedifferentiation and redifferentiation model, and a chondrocyte-to-osteoblast direct transdifferentiation model. These findings expand current understanding of chondrocyte origins and their fate during endochondral ossification. In the endochondral ossification process of fracture healing, chondrocytes, as core cells, coexist with a variety of cell types and crosstalk with each other in the callus. This article comprehensively describes the endochondral ossification models in the process of bone development and fracture healing with chondrocytes as the core. The signal pathways and key factors regulating chondrocyte differentiation, maturation, hypertrophy, apoptosis, dedifferentiation, and transdifferentiation into osteoblasts in different models are summarized.