Year: 2001
Type: article
Abstract: Most of the vertebrate skeleton forms by endochondral ossification, a multistep process that involves two successive cell-differentiation processes. Initially, following mesenchymal cell condensation, a cartilaginous scaffold forms that is later replaced by bone matrix. Under the control of transcription factors of the Sox family, these mesenchymal cells differentiate first into type II collagen–producing cells that proliferate until the shape of the future bone is established (1, 2). Subsequently, cells located at the center of this structure differentiate further to form hypertrophic chondrocytes, which synthesize a cartilaginous matrix that eventually calcifies. At the same time, the most mature hypertrophic chondrocytes undergo apoptosis, allowing the corresponding area to be invaded by blood vessels, and both multinucleate, matrix-resorbing cells and differentiated osteoblasts appear. The cartilaginous matrix is then degraded and replaced by a bone matrix secreted by osteoblasts.
Once this process is completed, the only cartilaginous structures remaining are the growth plate cartilages at the two distal ends of the bone. There, chondrocytes at each stage of differentiation — resting, proliferating, and hypertrophic chondrocytes — are arrayed in a linear succession from the most distal to the most medial regions. This growth plate cartilage therefore offers a powerful model for studying cell differentiation in situ.
Two mechanisms have been generally proposed to explain how chondrocytes and osteoblasts could emerge successively from the same mesenchymal condensation. First, two populations of progenitors might coexist within the condensations and differentiate along separate lineages into chondrocytes and osteoblasts. Alternatively, the same cells could differentiate along a single lineage, first generating chondrocytes, and later differentiating into osteoblasts. A second, related issue concerns the genetic regulation of the different steps of endochondral ossification, chondrogenesis, and bone morphogenesis. Mostly based on mouse genetic experiments, a number of recent studies, including the paper by Chung et al. (3) in a recent issue of the JCI, have established the cascade of events triggering each of these processes and have identified key factors required in their regulation (Figure (Figure11).
Figure 1
Molecular control of endochondral ossification. Transcription factors (Cbfa1 and others) promote the differentiation of the type II collagen–producing cells present in the skeletal mesenchymal condensations into Ihh-secreting hypertrophic chondrocytes. ...
DOI: 10.1172/jci12294
Author: Gerard Karsenty
Institution: Baylor College of Medicine
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1983496710