To the Editor:
The origin of the osteoblastic cells that produce trabecular bone has been unknown, with many cellular sources considered, including the hypertrophic chondrocytes.1 At the beginning of endochondral ossification, mesenchymal condensations that pre-figure the future long bones first develop into cartilage. As the cartilaginous template enlarges and becomes the shape of the future bone, chondrocytes in the central region stop proliferating, hypertrophy, and then die. The cartilaginous template is then invaded and transformed into the primary ossification center. The first committed osteoblast lineage cells appear in the perichondrium surrounding the mid-diaphyseal hypertrophic cartilage. Maes et al2 generated 2 transgenic mouse lines, using the Osterix and collagen I gene promoters to follow the fates of osteogenic cells during bone development. They found that the majority of the hypertrophic chondrocytes do not become osteoblasts.
Their data showed that mature chondrocytes do not detectably contribute to the osteoblast/osteocyte pool in the central metaphyseal region. Osteoblast precursors move into the developing primary ossification center and then differentiate into bone-forming trabecular osteoblasts. The entrance of the osteoblast precursors into the primary ossification center coincides with the initial invasion of blood vessels. Osteoblast precursors may differ from mature osteoblasts in that they, like vascular endothelial cells, are able to respond to migratory signals from vascular endothelial growth factor. Mature osteoblasts remain on the outside of the developing bone and generate cortical bone. They are retained on and within cortical bone surfaces.
The processes governing embryonic bone development are largely recapitulated during fracture healing, and Maes et al2 found that a similar co-invasion of osteoblast precursors and blood vessels occurs in the adult setting of bone repair. The infiltration of cartilaginous callus tissues by invading endothelium was closely associated with co-invasion of osteoblast precursors. Adult osteoblasts were markedly abundant in the peripheral portion of the callus.
The data indicate that perichondrial osteoblast lineage cells display differential destinies in developing bones. Osteoblast precursors predominantly move inside the bone to the trabecular region, while mature osteoblasts predominantly remain on the cortex.
Mark S. McMahon, MD
- Clarkin C, Olsen BR. On bone-forming cells and blood vessels in bone development. Cell Metab. 2010; 12(4):314–316. doi:10.1016/j.cmet.2010.09.009 [CrossRef]
- Maes C, Kobayashi T, Selig MK, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010; 19(2):329–344. doi:10.1016/j.devcel.2010.07.010 [CrossRef]