Matrix vesicles have a critical role in the initiation of mineral deposition in skeletal tissues, but the ways in which they exert this key function remain poorly understood. This issue is made even more intriguing by the fact that matrix vesicles are also present in nonmineralizing tissues. Thus, we tested the novel hypothesis that matrix vesicles produced and released by mineralizing cells are structurally and functionally different from those released by nonmineralizing cells. To test this hypothesis, we made use of cultures of chick embryonic hypertrophic chondrocytes in which mineralization was triggered by treatment with vitamin C and phosphate. Ultrastructural analysis revealed that both control nonmineralizing and vitamin C/phosphatetreated mineralizing chondrocytes produced and released matrix vesicles that exhibited similar round shape, smooth contour, and average size. However, unlike control vesicles, those produced by mineralizing chondrocytes had very strong alkaline phosphatase activity and contained annexin V, a membrane-associated protein known to mediate Ca2+ influx into matrix vesicles. Strikingly, these vesicles also formed numerous apatite-like crystals upon incubation with synthetic cartilage lymph, while control vesicles failed to do so. Northern blot and immunohistochemical analyses showed that the production and release of annexin V-rich matrix vesicles by mineralizing chondrocytes were accompanied by a marked increase in annexin V expression and, interestingly, were followed by increased expression of type I collagen. Studies on embryonic cartilages demonstrated a similar sequence of phenotypic changes during the mineralization process in vivo. Thus, chondrocytes located in the hypertrophic zone of chick embryo tibial growth plate were characterized by strong annexin V expression, and those located at the chondro–osseous mineralizing border exhibited expression of both annexin V and type I collagen. These findings reveal that hypertrophic chondrocytes can qualitatively modulate their production of matrix vesicles and only when induced to initiate mineralization, will release mineralization-competent matrix vesicles rich in annexin V and alkaline phosphatase. The occurrence of type I collagen in concert with cartilage matrix calcification suggests that the protein may facilitate crystal growth after rupture of the matrix vesicle membrane; it may also offer a smooth transition from mineralized type II/type X collagen-rich cartilage matrix to type I collagen-rich bone matrix.
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2 June 1997
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June 02 1997
Regulated Production of Mineralization-competent Matrix Vesicles in Hypertrophic Chondrocytes
Thorsten Kirsch,
Thorsten Kirsch
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
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Hyun-Duck Nah,
Hyun-Duck Nah
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
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Irving M. Shapiro,
Irving M. Shapiro
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
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Maurizio Pacifici
Maurizio Pacifici
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
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Thorsten Kirsch
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Hyun-Duck Nah
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Irving M. Shapiro
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Maurizio Pacifici
*Department of Anatomy and Histology, and ‡Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Please address all correspondence to Dr. Thorsten Kirsch, Department of Anatomy and Histology, School of Dental Medicine, University of Pennsylvania, 4001 Spruce Street, Philadelphia, PA 19104-6003. Tel.: (215) 5733502; Fax: (215) 573-2324.
Received:
September 25 1996
Revision Received:
December 09 1996
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 137 (5): 1149–1160.
Article history
Received:
September 25 1996
Revision Received:
December 09 1996
Citation
Thorsten Kirsch, Hyun-Duck Nah, Irving M. Shapiro, Maurizio Pacifici; Regulated Production of Mineralization-competent Matrix Vesicles in Hypertrophic Chondrocytes. J Cell Biol 2 June 1997; 137 (5): 1149–1160. doi: https://doi.org/10.1083/jcb.137.5.1149
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