Regulation of Chondrocyte Differentiation

  • Andreia M. Ionescu
  • M. Hicham Drissi
  • Regis J. O’Keefe


During the last decade, great progress has been made toward a better understanding of skeletal development, cartilage, and bone formation. In particular, many mechanisms underlying a variety of cellular and molecular processes that regulate growth and differentiation of chondrocytes, osteoblasts, and osteoclasts have been elucidated. This chapter will review some of the molecular and genetic pathways known to regulate cartilage development. Skeletal formation occurs through both endochondral and intramembraneous ossification. Flat bones and craniofacial bones are formed through intramembraneous ossification that relies on osteoblast differentiation directly from mesenchymal stem cells. The axial and appendicular skeleton form through endochondral ossification, which requires the formation of a cartilage intermediate that forms a template for osteoid deposition and bone formation. During endochondral bone formation, mesenchymal stem cells differentiate into both chondrocytes and osteoblasts. During development of the long bone, growth plates localize to either end of the skeletal element and the region of cartilage is surrounded by a perichondrium that is composed of undifferentiated mesenchymal cells. In the growth plates, chondrocytes undergo several stages of differentiation. One of the important transitions is from proliferation to hypertrophy, an event that precedes mineralization of the cartilage matrix (Fig. 1). Chondrocyte hypertrophy is characterized by profound physical and biochemical changes, including a 5- to 10fold increase in volume and expression of alkaline phosphatase, type X collagen, and MMP-1 3 (1,2). Type X collagen is a short-chain collagen found only in the hypertrophic zone of the growth plate. Although its exact function remains unclear, mutations in the colX gene have been found to cause Schmid metaphyseal chondrodysplasia (3), and transgenic mice with disruption in the colX gene exhibit a mild alteration of the growth plate architecture (4).


Growth Plate cAMP Response Element Binding Endochondral Ossification Chondrocyte Differentiation PTHrP Expression 
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© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Andreia M. Ionescu
  • M. Hicham Drissi
  • Regis J. O’Keefe

There are no affiliations available

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