Matrix vesicles and calcification
Abstract
Matrix vesicles (MVs) are extracellular, 100 nM in diameter, membrane-invested particles selectively located at sites of initial calcification in cartilage, bone, and predentin. The first crystals of apatitic bone mineral are formed within MVs close to the inner surfaces of their investing membranes. Matrix vesicle biogenesis occurs by polarized budding and pinching-off of vesicles from specific regions of the outer plasma membranes of differentiating growth plate chondrocytes, osteoblasts, and odontoblasts. Polarized release of MVs into selected areas of developing matrix determines the nonrandom distribution of calcification. Initiation of the first mineral crystals, within MVs (phase 1), is augmented by the activity of MV phosphatases (eg, alkaline phosphatase, adenosine triphosphatase and pyrophosphatase) plus calcium-binding molecules (eg, annexin I and phosphatidyl serine), all of which are concentrated in or near the MV membrane. Phase 2 of biologic mineralization begins with crystal release through the MV membrane, exposing preformed hydroxyapatite crystals to the extracellular fluid. The extracellular fluid normally contains sufficient Ca2+ and PO4(3-) to support continuous crystal proliferation, with preformed crystals serving as nuclei (templates) for the formation of new crystals by a process of homologous nucleation. In diseases such as osteoarthritis, crystal deposition arthritis, and atherosclerosis, MVs initiate pathologic calcification, which, in turn, augments disease progression.
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Mineralization of bone matrix takes place in two phases: the vesicular and the fibrillar phases.
“Thereafter, mineralization of bone matrix takes place into two phases: the vesicular and the fibrillar phases [40, 41].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [40]
Cites
Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein
Luo, G., Ducy, P. F., McKee, M. D., Pinero, G. J., Loyer, E. M., Behringer, R. R., & Karsenty, G. (1997) · Nature · doi:10.1038/386078a0 · Cited by 2,118 · see citing works
Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein
Vortkamp, A., Lee, K., Lanske, B., Segre, G. V., Kronenberg, H. M., & Tabin, C. J. (1996) · Science · doi:10.1126/science.273.5275.613 · Cited by 1,999 · see citing works
Bone morphogenetic proteins: multifunctional regulators of vertebrate development.Preprint
Hogan, B. L. M. (1996) · Genes & Development · doi:10.1101/gad.10.13.1580 · Cited by 1,964 · see citing works
VESICLES ASSOCIATED WITH CALCIFICATION IN THE MATRIX OF EPIPHYSEAL CARTILAGE
Anderson, H. C. (1969) · The Journal of Cell Biology · doi:10.1083/jcb.41.1.59 · Cited by 1,046 · see citing works
Self-citationRole of the Mouse ank Gene in Control of Tissue Calcification and Arthritis
Ho, A. M., Johnson, M. D., & Kingsley, D. M. (2000) · Science · doi:10.1126/science.289.5477.265 · Cited by 660 · see citing works
Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors
Low, M. G. (1987) · Biochemical Journal · doi:10.1042/bj2440001 · Cited by 596 · see citing works
Molecular Biology of Matrix Vesicles
Anderson, H. C. (1995) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-199505000-00034 · Cited by 585 · see citing works
Self-citationIsolation and Characterization of Calcifying Matrix Vesicles from Epiphyseal Cartilage
Ali, S. Y., Sajdera, S. W., & Anderson, H. C. (1970) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.67.3.1513 · Cited by 575 · see citing works
Self-citationImmunohistochemical localization of short chain cartilage collagen (type X) in avian tissues.
Schmid, T. M., & Linsenmayer, T. F. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.100.2.598 · Cited by 448 · see citing works
Okawa, A., Nakamura, I., Goto, S., Moriya, H., Nakamura, Y., & Ikegawa, S. (1998) · Nature Genetics · doi:10.1038/956 · Cited by 422 · see citing works
McCarty, D. J., Halverson, P. B., Carrera, G. F., et al. (1981) · Arthritis & Rheumatism · doi:10.1002/art.1780240303 · Cited by 310 · see citing works
Mechanism of Calcification: Inhibitory Role of Pyrophosphate
Fleisch, H. A., & Bisaz, S. (1962) · Nature · doi:10.1038/195911a0 · Cited by 276 · see citing works
Roach, H. I., Erenpreisa, J., & Aigner, T. G. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.2.483 · Cited by 275 · see citing works
Wolfe, F., & Sharp, J. T. (1998) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199809)41:9 · Cited by 274 · see citing works
Regulated Production of Mineralization-competent Matrix Vesicles in Hypertrophic Chondrocytes
Kirsch, T., Nah, H.-D., Shapiro, I. M., et al. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.5.1149 · Cited by 271 · see citing works
PHOSPHATASES OF EPIPHYSEAL CARTILAGE STUDIED BY ELECTRON MICROSCOPIC CYTOCHEMICAL METHODS
Matsuzawa, T., & Anderson, H. C. (1971) · Journal of Histochemistry & Cytochemistry · doi:10.1177/19.12.801 · Cited by 251 · see citing works
Self-citationBallock, R. T., Heydemann, A., Wakefield, L. M., et al. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1200 · Cited by 244 · see citing works
Ballock, R. T., & Reddi, A. H. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.126.5.1311 · Cited by 216 · see citing works
BMP-6 Is an Autocrine Stimulator of Chondrocyte Differentiation
Grimsrud, C. D., Romano, P. R., D’Souza, M., et al. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.4.475 · Cited by 185 · see citing works
The lipids of matrix vesicles from bovine fetal epiphyseal cartilage
Peress, N. S., Anderson, H. C., & Sajdera, S. W. (1974) · Calcified Tissue International · doi:10.1007/bf02060301 · Cited by 177 · see citing works
Self-citationWu, L., Genge, B. R., Lloyd, G. C., et al. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35301-2 · Cited by 163 · see citing works
Koyama, E., Golden, E. B., Kirsch, T., et al. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9207 · Cited by 139 · see citing works
Johnson, K., Moffa, A. B., Chen, Y., et al. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.6.883 · Cited by 136 · see citing works
Anderson, H. C., Hodges, P. T., Aguilera, X. M., Missana, L. R., & Moylan, P. E. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004801106 · Cited by 133 · see citing works
Self-citationDistribution of type X collagen mRNA in normal and osteoarthritic human cartilage
Hoyland, J. A., Thomas, J., Donn, R. P., et al. (1991) · Bone and Mineral · doi:10.1016/0169-6009(91)90005-k · Cited by 133 · see citing works
Farnum, C. E., & Wilsman, N. J. (1989) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100070505 · Cited by 115 · see citing works
Matrix vesicles are enriched in metalloproteinases that degrade proteoglycans
Dean, D. D., Schwartz, Z., Muniz, O. E., Gómez, R. S., Swain, L. D., Howell, D. S., & Boyan, B. D. (1992) · Calcified Tissue International · doi:10.1007/bf00301632 · Cited by 101 · see citing works
Inhibitory effects of basic fibroblast growth factor on chondrocyte differentiation
Wroblewski, J., & Edwall-Arvidsson, C. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100510 · Cited by 98 · see citing works
Tenenbaum, J., Muniz, O. E., Schumacher, H. R., et al. (1981) · Arthritis & Rheumatism · doi:10.1002/art.1780240307 · Cited by 87 · see citing works
Montessuit, C., Caverzasio, J., & Bonjour, J. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)55196-6 · Cited by 80 · see citing works
The relative importance of cysteine peptidases in osteoarthritis.
Lang, A., Hörler, D., & Baici, A. (2000) · PubMed · Cited by 73 · see citing works
Wuthier, R. E. (1973) · PubMed · Cited by 70 · see citing works
Arsenault, A. L., Frankland, B. W., & Ottensmeyer, F. P. (1991) · Calcified Tissue International · doi:10.1007/bf02555795 · Cited by 61 · see citing works
Kronenberg, H. M., Lee, K., Lanske, B., et al. (1997) · Journal of Endocrinology · doi:10.1677/joe.0.154s039 · Cited by 58 · see citing works
Role of proteoglycans in endochondral ossification: Inhibition of calcification
Dziewiatkowski, D. D., & Majznerski, L. L. (1985) · Calcified Tissue International · doi:10.1007/bf02557842 · Cited by 56 · see citing works
Hsu, H. H. T. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32684-x · Cited by 54 · see citing works
Matrix vesicle enzymes in human osteoarthritis
Einhorn, T. A., Gordon, S. L., Siegel, S. A., et al. (1985) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100030205 · Cited by 46 · see citing works
Neutral peptidase activities in matrix vesicles from bovine fetal alveolar bone and dog osteosarcoma
Hirschman, A. O. H., Deutsch, D., Hirschman, M., et al. (1983) · Calcified Tissue International · doi:10.1007/bf02405125 · Cited by 39 · see citing works
Expression of Bcl-2 protein in the epiphyseal plate cartilage and trabecular bone of growing rats
Wang, Y., Toury, R., Hauchecorne, M., et al. (1997) · Histochemistry and Cell Biology · doi:10.1007/s004180050145 · Cited by 38 · see citing works
Degradative enzyme systems in osteoarthritic cartilage
Ehrlich, M. G. (1985) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100030206 · Cited by 32 · see citing works
Uhthoff, H. K., & Sarkar, K. (1978) · International Orthopaedics · doi:10.1007/bf00266076 · Cited by 32 · see citing works
Xu, Y. J., Pritzker, K. P. H., & Cruz, T. F. (1994) · PubMed · Cited by 31 · see citing works
Kanabe, S., Hsu, H. H. T., Cecil, R. N. A., et al. (1983) · Journal of Histochemistry & Cytochemistry · doi:10.1177/31.4.6219157 · Cited by 29 · see citing works
Presence and specific concentration of carbonic anhydrase II in matrix vesicles
Stechschulte, D. J., Morris, D. C., Silverton, S. F., et al. (1992) · Bone and Mineral · doi:10.1016/0169-6009(92)90734-u · Cited by 28 · see citing works
Caswell, A. M., YOUSUFALI, S., & Russell, R. G. G. (1987) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(87)90023-7 · Cited by 27 · see citing works
Growth plate matrix vesicle biogenesis. The role of intracellular calcium.
Jp, I., Naidu, S., Noguchi, Y., et al. (1994) · PubMed · Cited by 26 · see citing works
The characterization of the tidemark in human articular cartilage
Dmitrovsky, E., Lane, L., & Bullough, P. G. (1978) · Metabolic Bone Disease and Related Research · doi:10.1016/0221-8747(78)90047-4 · Cited by 23 · see citing works
Matrix metalloproteinases in patients with osteoarthritis of the hip
Masuhara, K., Lee, S. B., Nakai, T., et al. (2000) · International Orthopaedics · doi:10.1007/s002640000110 · Cited by 23 · see citing works
Ultrastructure of the mineralizing metacarpophalangeal joint of progressive ankylosis (ank/ank) mice
Sampson, H. W. (1988) · American Journal of Anatomy · doi:10.1002/aja.1001820307 · Cited by 8 · see citing works
A Gene for Smooth-Running Joints
Hagmann, M. (2000) · Science · doi:10.1126/science.289.5477.225a · Cited by 6 · see citing works
(1981) · Arthritis & Rheumatism · doi:10.1002/art.1780240234 · Cited by 1 · see citing works
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Clarke, B. (2008) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04151206 · Cited by 2,192 · see citing works
Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044 · see citing works
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Hutcheson, J. D., Goettsch, C., Bertazzo, S., Maldonado, N., Ruiz, J. L., Goh, W., Yabusaki, K., Faits, T., Bouten, C., Franck, G., et al. (2016) · Nature Materials · doi:10.1038/nmat4519 · Cited by 419 · see citing works
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Huleihel, L., Hussey, G. S., Naranjo, J. D., Zhang, L., Dziki, J. L., Turner, N. J., Stolz, D. B., & Badylak, S. F. (2016) · Science Advances · doi:10.1126/sciadv.1600502 · Cited by 387 · see citing works
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- Authors
- Anderson, H. C.
- Affiliations
- University of Kansas Medical Center (US)
- Corresponding author
- Anderson, H. Clarke
- Venue
- Current Rheumatology Reports
- Published
- 2003-05
- Volume
- 5
- Issue
- 3
- Pages
- 222-226
- ISSN
- 1523-3774 (ISSN-L)
- 1534-6307
- OpenAlex
- W2137279952
- Cited by
- 606
- References
- 51
- Citations by year
- 2026: 27 · 2025: 23 · 2024: 26 · 2023: 24 · 2022: 35 · 2021: 39 · 2020: 49 · 2019: 29 · 2018: 40 · 2017: 35 · 2016: 28 · 2015: 26 · 2014: 29 · 2013: 27 · 2012: 29
- FWCI
- 8.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Rheumatology Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Dental and Craniofacial Research (DE 05262, R01DE005262)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Physical Sciences › Materials Science › Biomaterials › Calcium Carbonate Crystallization and Inhibition
- Keywords
- matrix vesicles, biomineralization, calcification, hydroxyapatite formation, growth plate chondrocytes, osteoblasts, odontoblasts, alkaline phosphatase, pyrophosphatase, annexin A1, phosphatidylserine, pathologic calcification, osteoarthritis, atherosclerosis
- MeSH terms
- Bone and Bones, Bone Matrix, Calcification, Physiologic, Clinical Trials as Topic, Growth Plate, Humans
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