Regulation of chondrogenesis and chondrocyte differentiation by stress
Michael J. Zuscik, … , Di Chen, Regis J. O’Keefe
Michael J. Zuscik, … , Di Chen, Regis J. O’Keefe
Published February 1, 2008
Citation Information: J Clin Invest. 2008;118(2):429-438. https://doi.org/10.1172/JCI34174.
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Regulation of chondrogenesis and chondrocyte differentiation by stress

Abstract

Chondrogenesis and endochondral ossification are the cartilage differentiation processes that lead to skeletal formation and growth in the developing vertebrate as well as skeletal repair in the adult. The exquisite regulation of these processes, both in normal development and in pathologic situations, is impacted by a number of different types of stress. These include normal stressors such as mechanical loading and hypoxia as well pathologic stressors such as injury and/or inflammation and environmental toxins. This article provides an overview of the processes of chondrogenesis and endochondral ossification and their control at the molecular level. A summary of the influence of the most well-understood normal and pathologic stressors on the differentiation program is also presented.

Authors

Michael J. Zuscik, Matthew J Hilton, Xinping Zhang, Di Chen, Regis J. O’Keefe

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Figure 1

Cellular events and molecular markers of chondrogenesis, chondrocyte differentiation, and AC development and maintenance.

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Cellular events and molecular markers of chondrogenesis, chondrocyte dif...
(A) Model of endochondral bone development beginning with mesenchymal cell condensation (i); chondrocyte differentiation and development of the cartilage template (ii); chondrocyte maturation and hypertrophy (iii); separation of cartilage growth regions, vascular invasion, and initiation of both cortical and trabecular bone (iv); and finally generation of the secondary center of ossification that separates AC and GP cartilage during postnatal bone development (v). MC, marrow cavity; 2°, secondary center of ossification. Red lines mark the vasculature, and yellow coloration marks mineralized bone. Black box outlines AC region magnified in B. (B) Graphical representation of the distinct cellular zones in postnatal AC. IZ, intermediate zone; RZ, radial zone; TM, tide mark; ZCC, zone of calcified cartilage; SB, subchondral bone; M, marrow. Vertical lines indicate zones of gene expression. (C) Model outlining the process of chondrogenesis and chondrocyte differentiation. Important markers at each stage of chondrocyte differentiation are listed below the stage at which the genes are expressed. Superscripts indicate the level of gene expression.