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. Author manuscript; available in PMC: 2017 Oct 1.
Published in final edited form as: Curr Opin Genet Dev. 2016 Jul 9;40:103–107. doi: 10.1016/j.gde.2016.06.012

Figure 1.

Figure 1

Stem cells for bone growth, maintenance and repair. (a) Limb bud formation. Prrx1+ cells in the lateral plate mesoderm are the precursors for all other mesenchymal cells in bones at a later stage. (b) Mesenchymal condensation. Sox9+ cells are the precursors for all other chondrocytes and osteoblasts therefore determine the domain for the future bones. (c) Cartilage formation. Condensing mesenchymal cells soon differentiate into chondrocytes (Sox9+, Col2+ and Acan+) and establish the growth cartilage. These cells proliferate and further differentiate into hypertrophic chondrocytes (ColX+) at the center of the mold. The osteogenic perichondrium forms in its vicinity, where the first osteoblasts precursors (Osx+) appear. (d) Ossification. Blood vessels invade into the cartilage template attracted by angiogenic factors secreted by hypertrophic chondrocytes. Primary ossification center (POC) is formed when perichondrial and other mesenchymal cells from the cartilage move inside with blood vessels and proliferate. (e) Growth. The growth plate provides the primary engine for bone growth, and multiple types of mesenchymal cells are enlisted to form bones. A subset of growth plate cells (Sox9+, Col2+ and Acan+) continues to provide bone cells, some of which may pass through a ColX+ stage. Cells in the metaphysis, including Osx+ and/or Grem1+ cells are the precursors for osteoblasts and bone marrow stromal cells including BMSCs (LepR+, Cxcl12+, PαS+ and Nes+). (f) Maintenance. After bone growth stops, BMSCs (LepR+ and others) become the main source of osteoblasts, bone marrow stromal cells and adipocytes. (g) Fracture repair. When a complete fracture occurs, two distinct stem cell populations from the periosteum and the bone marrow respond to injuries. Periosteal stem cells (Prrx1+ and/or aSMA+) are the major source of chondrocytes in the soft callus, although BMSCs can contribute to chondrocytes to some extent. (H) Soft callus. Chondrocytes in the soft callus (Acan+) are the source of osteoblasts in the repaired bone. (I) Ossification of the fracture callus.