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Matrix vesicles and calcification

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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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References and Recommended Reading

  1. Caswell AM, Ali SY, Russel RGG: Nucleoside triphosphate pyrophosphatase of rabbit matrix vesicles: a mechanism for the generation of inorganic pyrophosphate in epiphyseal cartilage. Biochim Biophys Acta 1987, 924:276–283.

    PubMed  CAS  Google Scholar 

  2. Fleisch H, Bisaz S: Mechanism of calcification: inhibitory role of pyrophosphate. Nature 1962, 195:911.

    Article  PubMed  CAS  Google Scholar 

  3. Dziewaitkowski DD, Majznerski LL: Role of proteoglycans in endochondral ossification: inhibition of calcification. Calcif Tiss Int 1985, 37:360–564.

    Google Scholar 

  4. Luo G, Ducy P, McKee MD, et al.: Spontaneous calcification of arteries and cartilage in mice lacking matrix Gla protein. Nature 1997, 386:78–81.

    Article  PubMed  CAS  Google Scholar 

  5. Anderson HC: Molecular biology of matrix vesicles. Clin Orthop Rel Res 1995, 314:266–280. Presents a brief but comprehensive and relatively up-to-date review of MV structure, molecular composition, and role in the mechanism of biomineralization.

    Google Scholar 

  6. Farnum CE, Wilsman NJ: Cellular turnover at the chondroosseous junction of growth plate cartilage: analysis of serial sections at the light microscopic level. J Orthop Res 1989, 7:654–666.

    Article  PubMed  CAS  Google Scholar 

  7. Dimitrovsky E, Lane LB, Bullough PG: The characterization of the tide mark in human articular cartilage. Met Bone Dis Rel Res 1978, 1:115–118.

    Article  Google Scholar 

  8. Matsuzawa T, Anderson HC: Phosphatases of epiphyseal cartilage studied by electron microscopic cytochemical methods. J Histochem Cytochem 1971, 19:801–808.

    PubMed  CAS  Google Scholar 

  9. Schmid TM, Linsenmayer TF: Immunolocalization of short chain cartilage collagen (type X) in Avian tissues. J Cell Biol 1985, 100:598–605.

    Article  PubMed  CAS  Google Scholar 

  10. Low MG: Biochemistry of the glycosylphosphatidyl inositol membrane protein anchors. Biochem J 1987, 244:1–13.

    PubMed  CAS  Google Scholar 

  11. Kronenberg HM, Lee K, Lanska B, Segre GV: Parathyroid hormone- related protein and Indian hedgehog control the pace of cartilage differentiation. J Endocrinol 1997, 154:S39-S45. A comprehensive description of the interaction of parathyroid hormone -related peptide and Indian hedgehog in growth plate by which the pace of cartilage differentiation is regulated.

    PubMed  CAS  Google Scholar 

  12. Wang Y, Toury R, Hauchecorne M, Balmain N: Expression of BCL-2 protein in the epiphyseal plate cartilage and trabecular bone of growing rats. Histochem Cell Biol 1997, 108:45–55.

    Article  PubMed  CAS  Google Scholar 

  13. Ballock RT, Heydemann A, Wakefield LM, et al.: TGF-b1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteinases. Dev Biol 1993, 158:414–429.

    Article  PubMed  CAS  Google Scholar 

  14. Wroblewski J, Edwall-Ardersson C: Inhibitory effects of basic fibroblast growth factor on chondrocyte differentiation. J Bone Min Res 1995, 10:735–742.

    Article  CAS  Google Scholar 

  15. Ballock RT, Reddi AH: Thyroxine is the serum factor that regulates morphogenesis of columnar cartilage from isolated chondrocytes in chemically defined medium. J Cell Biol 1994, 126:1311–1318.

    Article  PubMed  CAS  Google Scholar 

  16. Koyama S, Rolden EB, Kirsch T, et al.: Retinoid signaling is required for chondrocyte maturation and endochondral bone formation during limb skeletogenesis. Dev Biol 1999, 208:315–391.

    Article  Google Scholar 

  17. Vortkamp A, Kaechoong L, Lanske B, et al.: Regulation of rate of cartilage differentiation by Indian hedgehog and PTHrelated protein. Science 1996, 273:613–623. First demonstration of the negative feedback relationship between Indian hedgehog and parathyroid hormone-related peptide in promoting cartilage differentiation.

    Article  PubMed  CAS  Google Scholar 

  18. Grimsrud CD, Romeno PR, D’Souza N, et al.: BMP-6 is an autocrine stimulator of chondrocyte differentiation. J Bone Min Res 1999, 14:475–482. First demonstration that a negative feedback relationship exists in growth plate between BMP-6, which promotes chondrocyte differentiation, and parathyroid hormone-related peptide, which promotes proliferation and inhibits differentiation.

    Article  CAS  Google Scholar 

  19. Anderson HC: Vesicles associated with calcification in the matrix of epiphyseal cartilage. J Cell Biol 1969, 41:59–72.

    Article  PubMed  CAS  Google Scholar 

  20. Kirsch T, Mah H-D, Shapiro IM, Pacifici M: Regulated production of mineralization competent matrix vesicles in hypertrophic chondrocytes. J Cell Biol 1997, 137:1149–1160.

    Article  PubMed  CAS  Google Scholar 

  21. Dhanyamraju R, Sipe JB, Anderson HC: In vitro differentiation and matrix vesicle biogenesis in primary cultures of rat growth plate chondrocytes. In Proceedings of the First International Conference on Growth Plate. Edited by Anderson HC, Boyan B, Shapiro IM. 2002:In press.

  22. Joris I, Underwood JM, Kahn F, Majno G: Programmed cell death, oncosis and apoptosis: the case of growth cartilage. FASEB J 1998, 12:4618.

    Google Scholar 

  23. Iannotti JP, Naidu S, Noguchi Y, et al.: Growth plate matrix vesicle biogenesis: the role of intracellular calcium. Clin Orthop Rel Res 1994, 306:222–229.

    Google Scholar 

  24. Roach HI, Erenpreisa J, Aigner T: Osteogenic differentiation of hypertrophic chondrocytes involves asymmetric cell divisions and apoptosis. J Cell Biol 1995, 131:483–494.

    Article  PubMed  CAS  Google Scholar 

  25. Peress NS, Anderson HC, Sajdera SW: The lipids of matrix vesicles from bovine fetal epiphyseal cartilage. Calcif Tiss Res 1974, 14:275–281.

    Article  CAS  Google Scholar 

  26. Ali SY, Sajdera SW, Anderson HC: Isolation and characterization of calcifying matrix vesicles from epiphyseal cartilage. Proc Nat Acad Sci U S A 1970, 67:1513–1520.

    Article  CAS  Google Scholar 

  27. Kanabe S, Hsu HHT, Cecil RNA, Anderson HC: Electron microscopic localization of adenosine triphosphate (ATP) hydrolyzing activity in isolated matrix vesicles and reconstituted vesicles from calf cartilage. J Histochem Cytochem 1983, 31:462–470.

    PubMed  CAS  Google Scholar 

  28. Hsu HHT: Purification and partial characterization of ATPpyrophosphohydrolase from fetal bovine epiphyseal cartilage. J Biol Chem 1983, 258:3463–3464.

    PubMed  CAS  Google Scholar 

  29. Montessuit C, Caverzasio J, Bonjour JP: Characterization of a Pi transport system in cartilage matrix vesicles: potential role in the calcification process. J Biol Chem 1991, 266:17791–17797.

    PubMed  CAS  Google Scholar 

  30. Stechschulte DJ Jr, Morris DC, Silverton SF, et al.: Presence and specific concentration of carbonic anhydrase II in rat matrix vesicles. Bone Miner 1992, 17:187–191.

    Article  PubMed  CAS  Google Scholar 

  31. Wuthier RE: The role of phospholipids in biological calcification: distribution of phospholipase activity in calcifying epiphyseal cartilage. Clin Orthop 1973, 90:191–200.

    PubMed  Google Scholar 

  32. Hirschman A, Deutsch D, Hirschman M, et al.: Neutral peptidase activities in matrix vesicles from bovine fetal alveolar bone and dog osteosarcoma. Calcif Tiss Int 1983, 35:791–797.

    Article  CAS  Google Scholar 

  33. Dean DD, Schwartz Z, Muniz OE, et al.: Matrix vesicles are enriched in metalloproteinases that degrade proteoglycans. Calcif Tiss Int 1992, 50:342–349.

    Article  CAS  Google Scholar 

  34. Arsenault AL, Framkland BW, Ottensmeyer FP: Vectorial sequence of mineralization in the turkey leg tendon determined by electron microscopic imaging. Calcif Tiss Int 1991, 48:46–55.

    Article  CAS  Google Scholar 

  35. Wu LNY, Genge BR, Lloyd GC, Wuthier RE: Collagen binding proteins in collagenase-released matrix vesicles: specific binding of annexins, alkaline phosphatase, link proteins and hyaluronic acid binding region proteins to native cartilage collagens. J Biol Chem 1991, 266:1195–1203.

    PubMed  CAS  Google Scholar 

  36. Ali SY, Wisby A: Apatite crystal nodules in arthritic cartilage. Europ J Rheumatol Inflam 1978, 1:115–119.

    Google Scholar 

  37. Einhorn TA, Gordon SL, Siegel SA, et al.: Matrix vesicle enzymes in human osteoarthritis. J Orthop Res 1985, 3:170–184.

    Article  Google Scholar 

  38. Hoyland JA, Thomas JT, Denn R, et al.: Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage. Bone Miner 1991, 15:151–164.

    Article  PubMed  CAS  Google Scholar 

  39. Hashimoto S, Ochs RL, Komiza S, Lotz M: Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum 1998, 41:1632–1638.

    Article  PubMed  CAS  Google Scholar 

  40. Masuhara K, Lee SB, Makai T, et al.: Matrix metalloproteinases in patients with osteoarthritis of the hip. Int Orthop 2000, 24:92–96.

    Article  PubMed  CAS  Google Scholar 

  41. Lang A, Horler D, Baici A: The relative importance of cysteine peptidases in osteoarthritis. J Rheumatol 2000, 27:1970–1979.

    PubMed  CAS  Google Scholar 

  42. Anderson HC, Hodges PT, Aguilera XM, et al.: Bone morphogenetic protein localization in developing human and rat growth plate, metaphysis, epiphysis and articular cartilage. J Histochem Cytochem 2000, 48:1493–1502.

    PubMed  CAS  Google Scholar 

  43. Hogan BLM: Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 1996, 10:1580–1594.

    PubMed  CAS  Google Scholar 

  44. Missana LR, Aguilera XM, Hsu HHT, Anderson HC: Bone morphogenetic proteins (BMPs) and non-collagenous proteins of bone, identified in calcifying matrix vesicles of growth plate. J Bone Min Res 1998, 13:S241.

    Google Scholar 

  45. Johnson K, Moffa A, Chen Y, et al.: Matrix vesicle plasma membrane glycoprotein-1 regulates mineralization by murine osteoblastic MC3T3 cells. J Bone Min Res 1999, 14:883–892.

    Article  CAS  Google Scholar 

  46. Xu Y, Pritzger KP, Cruz TF: Characterization of chondrocyte alkaline phosphatase as a potential mediator in the dissolution of calcium pyrophosphate dehydrate crystals. J Rheumatol 1994, 21:912–919.

    PubMed  CAS  Google Scholar 

  47. Tenenbaum J, Muniz O, Schumacher HR, et al.: Comparison of phosphohydrolase activities from articular cartilage in calcium pyrophosphate deposition disease and primary arthritis. Arthritis Rheum 1981, 24:492–500.

    Article  PubMed  CAS  Google Scholar 

  48. Uhthoff HK, Sarkar K: Calcifying tendonitis: its pathogenetic mechanism and a rationale for its treatment. Int Orthop 1978, 2:187–193.

    Article  Google Scholar 

  49. McCarty DJ, Halverson PB, Carrera GF, et al.: Milwaukee shoulder: association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. Arthritis Rheum 1981, 24:264–473.

    Article  Google Scholar 

  50. Okawa A, Nakamura I, Goto S, et al.: Mutation in Npps in a mouse model of ossification of the posterior ligament of the spine. Nature Gen 1998, 19:271–273.

    Article  CAS  Google Scholar 

  51. Ho AM, Johnson MD, Kingsley DM: Role of the mouse ank gene in control of tissue calcification and arthritis. Science 2000, 289:225–226.

    Article  Google Scholar 

  52. Sampson HW: Ultrastructure of the mineralizing metacarpophalyngeal joint of progressive ankylosis (ank/ank) mice. Am J Anat 1988, 182:257–269.

    Article  PubMed  CAS  Google Scholar 

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Anderson, H.C. Matrix vesicles and calcification. Curr Rheumatol Rep 5, 222–226 (2003). https://doi.org/10.1007/s11926-003-0071-z

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