Skip to main content

Advertisement

Log in

Matrix vesicles are carriers of bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and noncollagenous matrix proteins

  • Short Communication
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Matrix vesicles (MVs) are well positioned in the growth plate to serve as a carrier of morphogenetic information to nearby chondrocytes and osteoblasts. Bone morphogenetic proteins (BMPs) carried in MVs could promote differentiation of these skeletal cells. Vascular endothelial growth factor (VEGF) in MVs could stimulate angiogenesis. Therefore, a study was undertaken to confirm the presence of bone morphogenetic protein (BMP)-1 through-7, VEGF, and the noncollagenous matrix proteins, bone sialoprotein (BSP), osteopontin (OPN), osteocalcin (OC), and osteonectin (ON) in isolated rat growth plate MVs. MVs were isolated from collagenase-digested rachitic rat tibial and femoral growth plates. The presence of BMP-1 through BMP-7, VEGF, BSP, ON, OPN, and OC was evaluated by Western blot, plus ELISA analyses for BMP-2 and-4 content. The alkaline phosphatase-raising ability of MV extracts on cultured rat growth plate chondrocytes was measured as a reflection of MV ability to promote chondroosseous differentiation. BMP-1 through-7, VEGF, BSP, ON, OPN, and OC were all detected by Western blot analyses. Chondrocytes treated with MV extracts showed a two-to threefold increase in alkaline phosphatase activity over control, indicating increased differentiation. Significant amounts of BMP-2 and BMP-4 were detected in MVs by ELISA. Combined, these data suggest that MVs could play an important morphogenetic role in growth plate and endochondral bone formation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Anderson HC, Garimella R, Tague SE (2005) The role of matrix vesicles in growth plate development and biomineralization. Front Biosci 10:822–837

    Article  PubMed  CAS  Google Scholar 

  2. Anderson HC, Reynolds JJ (1973) Pyrophosphate stimulation of calcium uptake into cultured embryonic bones. Fine structure of matrix vesicles and their role in calcification. Dev Biol 34:211–227

    Article  PubMed  CAS  Google Scholar 

  3. Slavkin HC, Croissant R, Bringas P Jr (1972) Epithelialmesenchymal interactions during odontogenesis. 3. A simple method for the isolation of matrix vesicles. J Cell Biol 53: 841–849

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Missana LR, Aguilera XM, Hsu HHT, Anderson HC (1998) Bone morphogenetic proteins (BMPs) and non-collagenous proteins of bone identified in calcifying matrix vesicles of growth plate. Bone (NY) 23(suppl):S241

    Google Scholar 

  6. Nakase T, Yoshikawa H (2006) Potential roles of bone morphogenetic proteins (BMPs) in skeletal repair and regeration. J Bone Miner Metab 24(6):425–433

    Article  PubMed  Google Scholar 

  7. Nakagawa T, Sugiyama T, Kamei T, Murata T, Tagawa T (2001) An immuno-light-and electron-microscopic study of the expression of bone morphogenetic protein-2 during the process of ectopic bone formation in the rat. Arch Oral Biol 46:403–411

    Article  PubMed  CAS  Google Scholar 

  8. Nahar NN, Missana LR, Garimella R, Tague S, Anderson HC (2005) Matrix vesicles are carriers of bone morphogenetic proteins (BMPs) and non-collagenous matrix proteins J Bone Miner Res 20(suppl 1):S321

    Google Scholar 

  9. Anderson HC, Hodges PT, Aguilera XM, Missana L, Moylan PE (2000) Bone morphogenetic protein (BMP) localization in developing human and rat growth plate, metaphysis, epiphysis, and articular cartilage. J Histochem Cytochem 48:1493–1502

    PubMed  CAS  Google Scholar 

  10. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628

    Article  PubMed  CAS  Google Scholar 

  11. Horner A, Bishop NJ, Bord S, Beeton C, Kelsall AW, Coleman N, Compston JE (1999) Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage. J Anat 194(pt 4):519–524

    Article  PubMed  CAS  Google Scholar 

  12. Hunter GK, Goldberg HA (1993) Nucleation of hydroxyapatite by bone sialoprotein. Proc Natl Acad Sci U S A 90:8562–8565

    Article  PubMed  CAS  Google Scholar 

  13. Cooper LF, Yliheikkila PK, Felton DA, Whitson SW (1998) Spatiotemporal assessment of fetal bovine osteoblast culture differentiation indicates a role for BSP in promoting differentiation. J Bone Miner Res 13:620–632

    Article  PubMed  CAS  Google Scholar 

  14. Gordon JAR, Tye CE, Sapaio AV, Underhill TM, Hunter GK, Goldberg HA (2007) Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in Vitro. Bone (NY) 41:462–473

    CAS  Google Scholar 

  15. Wang J, Zhou HY, Salih E, Xu L, Wunderlich L, Gu X, Hofstaetter JG, Torres M, Glimcher MJ (2006) Site-specific in vivo calcification and osteogenesis stimulated by bone sialoprotein. Calcif Tissue Int 79:179–189

    Article  PubMed  CAS  Google Scholar 

  16. Menanteau J, Neuman WF, Newman MW (1982) A study of bone proteins which can prevent hydroxyapatite formation. Metab Bone Dis Relat Res 1982;4(2):157–162

    Article  Google Scholar 

  17. Boskey AL, Maresca M, Ullrich W, Doty SB, Butler WT, Prince CW (1993) Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel. Bone Miner 22:147–159

    Article  PubMed  CAS  Google Scholar 

  18. Boskey AL, Spevak L, Paschalis E, Doty SB, McKee MD (2002) Osteopontin deficiency increases mineral content and mineral crystallinity in mouse bone. Calcif Tissue Int 71:145–154

    Article  PubMed  CAS  Google Scholar 

  19. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature (Lond) 382:448–452

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Anderson HC, Stechschulte DJ Jr, Collins DE, Jacobs DH, Morris DC, Hsu HH, Redford PA, Zeiger S (1990) Matrix vesicle biogenesis in vitro by rachitic and normal rat chondrocytes. Am J Pathol 136:391–398

    PubMed  CAS  Google Scholar 

  22. Garimella R, Sipe JB, Anderson HC (2004) A simple and non-radioactive technique to study the effect of monophosphoesters on matrix vesicle-mediated calcification. Biol Proc Online 6:263–267

    Article  CAS  Google Scholar 

  23. Garimella R, Bi X, Camacho N, Sipe JB, Anderson HC (2004) Primary culture of rat growth plate chondrocytes: an in vitro model of growth plate histotype, matrix vesicle biogenesis and mineralization. Bone (NY) 34:961–970

    CAS  Google Scholar 

  24. Anderson HC, Reynolds PR, Hsu HH, Missana L, Masuhara K, Moylan PE, Roach HI (2002) Selective synthesis of bone morphogenetic proteins-1,-3,-4 and bone sialoprotein may be important for osteoinduction by Saos-2 cells. J Bone Miner Metab 20:73–82

    Article  PubMed  CAS  Google Scholar 

  25. Daluiski A, Engstrand T, Bahamonde ME, Gamer LW, Agius E, Stevenson SL, Cox K, Rosen V, Lyons KM (2001) Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet 27:84–88

    PubMed  CAS  Google Scholar 

  26. Chubinskaya S, Merrihew C, Cs-Szabo G, Mollenhauer J, McCartney J, Rueger DC, Kuettner KE (2000) Human articular chondrocytes express osteogenic protein-1. J Histochem Cytochem 48:239–250

    PubMed  CAS  Google Scholar 

  27. Jones WK, Richmond EA, White K, Sasak H, Kusmik W, Smart J, Oppermann H, Rueger DC, Tucker RF (1994) Osteogenic protein-1 (OP-1) expression and processing in Chinese hamster ovary cells: isolation of a soluble complex containing the mature and pro-domains of OP-1. Growth Factors 11:215–225

    Article  PubMed  CAS  Google Scholar 

  28. Wordinger RJ, Agarwal R, Talati M, Fuller J, Lambert W, Clark AF (2002) Expression of bone morphogenetic proteins (BMP), BMP receptors, and BMP associated proteins in human trabecular meshwork and optic nerve head cells and tissues. Mol Vis 8:241–250

    PubMed  CAS  Google Scholar 

  29. Janitz M, Heiser V, Bottcher U, Landt O, Lauster R (1998) Three alternatively spliced variants of the gene coding for the human bone morphogenetic protein-1. J Mol Med 76:141–146

    Article  PubMed  CAS  Google Scholar 

  30. Hauschka PV, Frenkel J, DeMuth R, Gundberg CM (1983) Presence of osteocalcin and related higher molecular weight 4-carboxyglutamic acid-containing proteins in developing bone. J Biol Chem 258:176–182

    PubMed  CAS  Google Scholar 

  31. Kanim LEA, Bae H, Zhao L, et al (2003) Inter and intravariability of BMPs in commercially available demineralized bone matrices. In: Proceedings of the North American Spine Society 18th Annual Meeting. Spine J 32:81S

    Google Scholar 

  32. Blum B, Moseley J, Miller L, Richelsoph K, Haggard W (2004) Measurement of bone morphogenetic proteins and other growth factors in demineralized bone matrix. Orthopedics 27:s161–s165

    PubMed  Google Scholar 

  33. Pietrzak WS, Woodell-May J, McDonald N (2006) Assay of bone morphogenetic protein-2,-4, and-7 in human demineralized bone matrix. J Craniofac Surg 17:84–90

    Article  PubMed  Google Scholar 

  34. Enomoto-Iwamoto M, Iwamoto M, Mukudai Y, Kawakami Y, Nohno T, Higuchi Y, Takemoto S, Ohuchi H, Noji S, Kurisu K (1998) Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes. J Cell Biol 140:409–418

    Article  PubMed  CAS  Google Scholar 

  35. Grimsrud CD, Romano PR, D’souza M, Puzas JE, Schwarz EM, Reynolds PR, Roiser RN, O’Keefe RJ (2001) BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog. J Orthop Res 19:18–25

    Article  PubMed  CAS  Google Scholar 

  36. Leboy PS, Sullivan TA, Nooreyazdan M, Venezian RA (1997) Rapid chondrocyte maturation by serum-free culture with BMP-2 and ascorbic acid. J Cell Biochem 66:394–403

    Article  PubMed  CAS  Google Scholar 

  37. Kaneko H, Arakawa T, Mano H, Kaneda T, Ogasawara A, Nakagawa M, Toyama Y, Yabe Y, Kumegawa M, Hakeda Y (2000) Direct stimulation of osteoclastic bone resorption by bone morphogenetic protein (BMP)-2 and expression of BMP receptors in mature osteoclasts. Bone (NY) 27:479–486

    CAS  Google Scholar 

  38. Garimella R, Tague SE, Zhang J, Belibi F, Nahan N, Sun BH, Insogna K, Wang J, Anderson HC (2008) Expression and synthesis of bone morphogenetic proteins by osteoclasts: a possible path to anabolic bone remodeling. J Histochem Cytochem 56:569–577

    Article  PubMed  CAS  Google Scholar 

  39. Dvorak HF (2002) Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 20:4368–4380

    Article  PubMed  CAS  Google Scholar 

  40. Asou Y, Rittling SR, Yoshitake H, Tsuji K, Shinomiya K, Nifuji A, Denhardt DT, Noda M (2001) Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone. Endocrinology 142:1325–1332

    Article  PubMed  CAS  Google Scholar 

  41. Hunter GK, Hauschka PV, Poole AR, Rosenberg LC, Goldberg HA (1996) Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 317(pt 1):59–64

    PubMed  CAS  Google Scholar 

  42. Xiao Z, Camalier CE, Nagashima K, Chan KC, Lucas DA, de la Cruz MJ, Gignac M, Lockett S, Issaq HJ, Veenstra TD, Conrads TP, Beck GR Jr (2007) Analysis of the extracellular matrix vesicle proteome in mineralizing osteoblasts. J Cell Physiol 210:325–335

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. Clarke Anderson.

About this article

Cite this article

Nahar, N.N., Missana, L.R., Garimella, R. et al. Matrix vesicles are carriers of bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and noncollagenous matrix proteins. J Bone Miner Metab 26, 514–519 (2008). https://doi.org/10.1007/s00774-008-0859-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-008-0859-z

Key words

Navigation