Skip to main content

Advertisement

SpringerLink
Log in

S100A8/S100A9 and their association with cartilage and bone

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

S100A8 and S100A9 are calcium-binding proteins expressed in myeloid cells and are markers of numerous inflammatory diseases in humans. S100A9 has been associated with dystrophic calcification in human atherosclerosis. Here we demonstrate S100A8 and S100A9 expression in murine and human bone and cartilage cells. Only S100A8 was seen in preosteogenic cells whereas osteoblasts had variable, but generally weak expression of both proteins. In keeping with their reported high-mRNA expression, S100A8 and S100A9 were prominent in osteoclasts. S100A8 was expressed in alkaline phosphatase-positive hypertrophic chondrocytes, but not in proliferating chondrocytes within the growth plate where the cartilaginous matrix was calcifying. S100A9 was only evident in the invading vascular osteogenic tissue penetrating the degenerating chondrocytic zone adjacent to the primary spongiosa, where S100A8 was also expressed. Whilst, S100A8 has been shown to be associated with osteoblast differentiation, both S100A8 and S100A9 may contribute to calcification of the cartilage matrix and its replacement with trabecular bone, and to regulation of redox in bone resorption.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Alini M, Marriott A, Chen T, Abe S, Poole AR (1996) A novel angiogenic molecule produced at the time of chondrocyte hypertrophy during endochondral bone formation. Dev Biol 176:124–132

    Article  CAS  PubMed  Google Scholar 

  • Al-Rasheed A, Scheerens H, Rennick DM, Fletcher HM, Tatakis DN (2003) Accelerated alveolar bone loss in mice lacking interleukin-10. J Dent Res 82:632–635

    CAS  PubMed  Google Scholar 

  • Balmain N, Moutahir F, Heizmann CW, Lieberherr M (2003) Immunolocalization of S100A2 calcium-binding protein in cartilage and bone cells. Cell Mol Biol (Noisy-le-grand) 49:485–486

    CAS  Google Scholar 

  • Chayen J, Bitensky L (1981) Cytochemistry in the bioassay of hormones. J Clin Pathol 34:575–588

    Article  CAS  PubMed  Google Scholar 

  • Cornish CJ, Devery JM, Poronnik P, Lackmann M, Cook DI, Geczy CL (1996) S100 protein CP-10 stimulates myeloid cell chemotaxis without activation. J Cell Physiol 166:427–437

    Article  CAS  PubMed  Google Scholar 

  • Donato R (2001) S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33:637–668

    Article  CAS  PubMed  Google Scholar 

  • Duarte WR, Shibata T, Takenaga K, Takahashi E, Kubota K, Ohya K, Ishikawa I, Yamauchi M, Kasugai S (2003) S100A4: a novel negative regulator of mineralization and osteoblast differentiation. J Bone Miner Res 18:493–501

    Article  CAS  PubMed  Google Scholar 

  • Engelkamp D, Schafer BW, Mattei MG, Erne P, Heizmann CW (1993) Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. Proc Natl Acad Sci U S A 90:6547–6551

    Article  CAS  PubMed  Google Scholar 

  • Engsig MT, Chen QJ, Vu TH, Pedersen AC, Therkidsen B, Lund LR, Henriksen K, Lenhard T, Foged NT, Werb Z, Delaisse JM (2000) Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones. J Cell Biol 151:879–889

    Article  CAS  PubMed  Google Scholar 

  • Foell D, Hernandez-Rodriguez J, Sanchez M, Vogl T, Cid MC, Roth J (2004) Early recruitment of phagocytes contributes to the vascular inflammation of giant cell arteritis. J Pathol 204:311–316

    Article  CAS  PubMed  Google Scholar 

  • Gronthos S, Zannettino AC, Graves SE, Ohta S, Hay SJ, Simmons PJ (1999) Differential cell surface expression of the STRO-1 and alkaline phosphatase antigens on discrete developmental stages in primary cultures of human bone cells. J Bone Miner Res 14(1):47–56

    Article  CAS  PubMed  Google Scholar 

  • Gronthos S, Zannettino AC, Hay SJ, Shi S, Graves SE, Kortesidis A, Simmons PJ (2003) Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J Cell Sci 116:1827–1835

    Article  CAS  PubMed  Google Scholar 

  • Hadjigogos K (2003) The role of free radicals in the pathogenesis of rheumatoid arthritis. Panminerva Med 45:7–13

    CAS  PubMed  Google Scholar 

  • Harrison CA, Raftery MJ, Walsh J, Alewood P, Iismaa SE, Thliveris S, Geczy CL (1999) Oxidation regulates the inflammatory properties of the murine S100 protein S100A8. J Biol Chem 274:8561–8569

    Article  CAS  PubMed  Google Scholar 

  • Helfman DM, Kim EJ, Lukanidin E, Grigorian M (2005) The metastasis associated protein S100A4: role in tumour progression and metastasis. Br J Cancer 92:1955–1958

    Article  CAS  PubMed  Google Scholar 

  • Hobbs JA, May R, Tanousis K, McNeill E, Mathies M, Gebhardt C, Henderson R, Robinson MJ, Hogg N (2003) Myeloid cell function in MRP-14 (S100A9) null mice. Mol Cell Biol 23:2564–2576

    Article  CAS  PubMed  Google Scholar 

  • Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901

    Article  CAS  PubMed  Google Scholar 

  • Iismaa SE, Hu S, Kocher M, Lackmann M, Harrison CA, Thliveris S, Geczy CL (1994) Recombinant and cellular expression of the murine chemotactic protein, CP-10. DNA Cell Biol 13:183–192

    Article  CAS  PubMed  Google Scholar 

  • Kerkhoff C, Nacken W, Benedyk M, Dagher MC, Sopalla C, Doussiere J (2005) The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2. Faseb J 19:467–469

    CAS  PubMed  Google Scholar 

  • Laboux O, Ste-Marie LG, Glorieux FH, Nanci A (2003) Quantitative immunogold labeling of bone sialoprotein and osteopontin in methylmethacrylate-embedded rat bone. J Histochem Cytochem 51(1):61–67

    CAS  PubMed  Google Scholar 

  • Lee ER, Lamplugh L, Shepard NL, Mort JS (1995) The septoclast, a cathepsin B-rich cell involved in the resorption of growth plate cartilage. J Histochem Cytochem 43:525–536

    CAS  PubMed  Google Scholar 

  • Lee K, Lanske B, Karaplis AC, Deeds JD, Kohno H, Nissenson RA, Kronenberg HM, Segre GV (1996) Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development. Endocrinology 137:5109–5118

    Article  CAS  PubMed  Google Scholar 

  • Liu AL, Zhang ZM, Zhu BF, Liao ZH, Liu Z (2004) Metallothionein protects bone marrow stromal cells against hydrogen peroxide-induced inhibition of osteoblastic differentiation. Cell Biol Int 28:905–911

    Article  CAS  PubMed  Google Scholar 

  • Makino E, Sakaguchi M, Iwatsuki K, Huh NH (2004) Introduction of an N-terminal peptide of S100C/A11 into human cells induces apoptotic cell death. J Mol Med 82:612–620

    Article  CAS  PubMed  Google Scholar 

  • Manitz MP, Horst B, Seeliger S, Strey A, Skryabin BV, Gunzer M, Frings W, Schonlau F, Roth J, Sorg C, Nacken W (2003) Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro. Mol Cell Biol 23:1034–1043

    Article  CAS  PubMed  Google Scholar 

  • McCormick MM, Rahimi F, Bobryshev YV, Gaus K, Zreiqat H, Cai H, Lord RS, Geczy CL (2005) S100A8 and S100A9 in human arterial wall: Implications for atherogenesis. J Biol Chem 280(50):41521–41529

    Article  CAS  PubMed  Google Scholar 

  • McNutt NS (1998) The S100 family of multipurpose calcium-binding proteins. J Cutan Pathol 25:521–529

    Article  CAS  PubMed  Google Scholar 

  • Moses MA, Wiederschain D, Wu I, Fernandez CA, Ghazizadeh V, Lane WS, Flynn E, Sytkowski A, Tao T, Langer R (1999) Troponin I is present in human cartilage and inhibits angiogenesis. Proc Natl Acad Sci U S A 96:2645–2650

    Article  CAS  PubMed  Google Scholar 

  • Passey RJ, Williams E, Lichanska AM, Wells C, Hu S, Geczy CL, Little MH, Hume DA (1999b) A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. J Immunol 163:2209–2216

    CAS  PubMed  Google Scholar 

  • Passey RJ, Xu K, Hume DA, Geczy CL (1999a) S100A8: emerging functions and regulation. J Leukoc Biol 66:549–556

    CAS  PubMed  Google Scholar 

  • Raftery MJ, Yang Z, Valenzuela SM, Geczy CL (2001) Novel intra- and inter-molecular sulfinamide bonds in S100A8 produced by hypochlorite oxidation. J Biol Chem 276:33393–33401

    Article  CAS  PubMed  Google Scholar 

  • Rahimi F, Hsu K, Endoh Y, Geczy CL (2005) FGF-2, IL-1beta and TGF-beta regulate fibroblast expression of S100A8. Febs J 272:2811–2827

    Article  CAS  PubMed  Google Scholar 

  • Ravasi T, Hsu K, Goyette J, Schroder K, Yang Z, Rahimi F, Miranda LP, Alewood PF, Hume DA, Geczy C (2004) Probing the S100 protein family through genomic and functional analysis. Genomics 84:10–22

    Article  CAS  PubMed  Google Scholar 

  • Roth J, Vogl T, Sorg C, Sunderkotter C (2003) Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol 24:155–158

    Article  CAS  PubMed  Google Scholar 

  • Shukunami C, Iyama K, Inoue H, Hiraki Y (1999) Spatiotemporal pattern of the mouse chondromodulin-I gene expression and its regulatory role in vascular invasion into cartilage during endochondral bone formation. Int J Dev Biol 43:39–49

    CAS  PubMed  Google Scholar 

  • Sorci G, Riuzzi F, Agneletti AL, Marchetti C, Donato R (2003) S100B inhibits myogenic differentiation and myotube formation in a RAGE-independent manner. Mol Cell Biol 23:4870–4881

    Article  CAS  PubMed  Google Scholar 

  • Sorci G, Riuzzi F, Agneletti AL, Marchetti C, Donato R (2004) S100B causes apoptosis in a myoblast cell line in a RAGE-independent manner. J Cell Physiol 199:274–283

    Article  CAS  PubMed  Google Scholar 

  • Stewart K, Walsh S, Screen J, Jefferiss CM, Chainey J, Jordan GR, Beresford JN (1999) Further characterization of cells expressing STRO-1 in cultures of adult human bone marrow stromal cells. J Bone Miner Res 14(8):1345–1356

    Article  CAS  PubMed  Google Scholar 

  • Stickens D, Behonick DJ, Ortega N, Heyer B, Hartenstein B, Yu Y, Fosang AJ, Schorpp-Kistner M, Angel P, Werb Z (2004) Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development 131:5883–5895

    Article  CAS  PubMed  Google Scholar 

  • Viemann D, Goebeler M, Schmid S, Klimmek K, Sorg C, Ludwig S, Roth J (2004) Transcriptional profiling of IKK2/NF-kappa B- and p38 MAP kinase-dependent gene expression in TNF-alpha-stimulated primary human endothelial cells. Blood 103:3365–3373

    Article  CAS  PubMed  Google Scholar 

  • Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, Foell D, Gerke V, Manitz MP, Nacken W, Werner S, Sorg C, Roth J (2004) MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood 104:4260–4268

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Middleton F, Horton JA, Reichel L, Farnum CE, Damron TA (2004) Microarray analysis of proliferative and hypertrophic growth plate zones identifies differentiation markers and signal pathways. Bone 35:1273–1293

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Tao T, Raftery MJ, Youssef P, Di Girolamo N, Geczy CL (2001) Proinflammatory properties of the human S100 protein S100A12. J Leukoc Biol 69:986–994

    CAS  PubMed  Google Scholar 

  • Yen T, Harrison CA, Devery JM, Leong S, Iismaa SE, Yoshimura T, Geczy CL (1997) Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli. Blood 90:4812–4821

    CAS  PubMed  Google Scholar 

  • Zreiqat H, Markovic B, Walsh WR, Howlett CR (1996) A novel technique for quantitative detection of mRNA expression in human bone derived cells cultured on biomaterials. J Biomed Mater Res 33:217–223

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge the Australia National Health and Medical Research Council and the Australian Research Council. We thank Mrs. Barbara James for preparing all the bone sections and histological staining. We thank Associate Professors Christopher Little and Brian Freeman for their editorial assistance and valuable comments during the preparation of this manuscript. We thank Professor Boskey and colleagues for their discussion on nucleation studies.

Author information

Authors and Affiliations

  1. Biomaterials and Tissue Engineering Research Unit, Biomedical Engineering, School of AMME, The University of Sydney, Sydney, NSW, 2006, Australia

    H. Zreiqat

  2. Inflammatory Diseases Research Unit, School of Medical Sciences, University of NSW, Sydney, NSW, 2052, Australia

    C. R. Howlett & C. L. Geczy

  3. Mesenchymal Stem Cell Group, Institute of Medical and Veterinary Science/Hanson Institute, Adelaide, SA, 2005, Australia

    S. Gronthos

  4. Institute for Molecular Bioscience, University of Queensland, Queensland, QLD, 4072, Australia

    D. Hume

Authors
  1. H. Zreiqat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. R. Howlett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Gronthos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Hume
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. L. Geczy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Zreiqat.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zreiqat, H., Howlett, C.R., Gronthos, S. et al. S100A8/S100A9 and their association with cartilage and bone. J Mol Hist 38, 381–391 (2007). https://doi.org/10.1007/s10735-007-9117-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-007-9117-2

Keywords

Search

Navigation