Bone wound healing after surgical drilling/cutting initially involves a typical inflammatory response with a leukocyte-rich cell infiltrate whose professional phagocytes (neutrophils and macrophages) clear the wound site of various bacterial (if present), particulate, and insoluble components arising from the original wounding event. As part of this process, in a surgical model of bone repair in rats, osteopontin (OPN) secreted by macrophages – with its known mineral-binding properties arising from abundant calcium-binding phosphorylations and overall net negative charge – binds to the newly exposed mineralized surfaces of particulate bone debris and the osseous wound margins created by the drilling, as shown by high-resolution immunogold labeling and transmission electron microscopy. For bone debris powder, OPN serves as an opsonin for clearance by macrophage phagocytosis, as demonstrated in vitro by phagocytosis assays using cultured J774.A1 murine macrophages and OPN-coated microbeads. Macrophage-secreted OPN binding to the bone wound margins contributes to cement line (plane) formation with subsequent OPN additions to the cement line coming from osteoblast lineage cells arriving at this site to effect bone repair upon further osteoblast differentiation, and extracellular matrix deposition and mineralization. Such interfacial OPN is thought to contribute to the cell adhesion, cell signaling, and matrix mineralization events required to effectively integrate the new bone into the preexisting bone at the margins of the drill site.

Keywords:
Macrophage, Osteoblast, Osteopontin, Bone wound healing, Phagocytosis, Opsonization
1.
Azzopardi, P.V., J. O’Young, G. Lajoie, M. Karttunen, H.A. Goldberg, G.K. Hunter (2010) Roles of electrostatics and conformation in protein-crystal interactions. PLoS One 5: e9330.
2.
Beuth J., H.L. Ko, G. Pulverer, G. Uhlenbruck, H. Pichlmaier (1995) Importance of lectins for the prevention of bacterial infections and cancer metastases. Glycoconj J 2: 1–6.
3.
Bonewald, L.F. (2007) Osteocytes as dynamic multifunctional cells. Ann NY Acad Sci 1116: 281–290.
4.
Boskey, A.L. (1995) Osteopontin and related phosphorylated sialoproteins: effects on mineralization. Ann NY Acad Sci 760: 249–256.
5.
Djaldetti, M., H. Salman, M. Bergman, R. Djaldetti, H. Bessler (2002) Phagocytosis – the mighty weapon of the silent warriors. Microsc Res Tech 57: 421–431.
6.
Fearon, D.T., K.F. Austen (1980) Current concepts in immunology: the alternative pathway of complement – a system for host resistance to microbial infection. N Engl J Med 303: 259–263.
7.
Fisher, L.W., N.S. Fedarko (2003) Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Connect Tissue Res 44(suppl 1): 33–40.
8.
Kaartinen, M.T., S. El-Maadawy, N.H. Rasanen, M.D. McKee (2002) Tissue transglutaminase and its substrates in bone. J Bone Miner Res 17: 2161–2173.
9.
Liaw, L., D.E. Birk, C.B. Ballas, J.S. Whitsitt, J.M. Davidson, B.L. Hogan (1998) Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 101: 1468–1478.
10.
Lund, S.A., C.M. Giachelli, M. Scatena (2009) The role of osteopontin in inflammatory processes. J Cell Commun Signal 3: 311–322.
11.
McKee, M.D., W.N. Addison, M.T. Kaartinen (2005) Hierarchies of extracellular matrix and mineral organization in bone of the craniofacial complex and the skeleton. Cells Tissues Organs 181: 176–188.
12.
McKee, M.D., A. Nanci (1996a) Osteopontin at mineralized tissue interfaces in bone, teeth and osseointegrated implants: ultrastructural distribution and implications for mineralized tissue formation, turnover and repair. Microsc Res Tech 33: 141–164.
13.
McKee, M.D., A. Nanci (1996b) Secretion of osteopontin by macrophages and its accumulation at tissue surfaces during wound healing in mineralized tissues: a potential requirement for macrophage adhesion and phagocytosis. Anat Rec 245: 394–409.
14.
McKee, M.D., A. Nanci (1996c) Osteopontin: an interfacial extracellular matrix protein in mineralized tissues. Connect Tissue Res 35: 197–205.
15.
Moester, M.J., S.E. Papapoulos, C.W. Löwik, R.L. van Bezooijen (2010) Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 87: 99–107.
16.
Murry, C.E., C.M. Giachelli, S.M. Schwartz, R. Vracko (1994) Macrophages express osteopontin during repair of myocardial necrosis. Am J Pathol 145: 1450–1562.
17.
Pampena, D.A., K.A. Robertson, O. Litvinova, G. Lajoie, H.A. Goldberg, G.K. Hunter (2004) Inhibition of hydroxyapatite formation by osteopontin phosphopeptides. Biochem J 378: 1083–1087.
18.
Pedraza, C.E., L.G. Nikolcheva, M.T. Kaartinen, J.E. Barralet, M.D. McKee (2008) Osteopontin functions as an opsonin and facilitates phagocytosis by macrophages of hydroxyapatite-coated microspheres: implications for bone wound healing. Bone 43: 708–716.
19.
Van Oss, C.J., C.F. Gillman (1972) Phagocytosis as a surface phenomenon. 2. Contact angles and phagocytosis of encapsulated bacteria before and after opsonization by specific antiserum and complement. J Reticuloendothel Soc 12: 497–502.
20.
Vieira, O.V., R.J. Botelho, S. Grinstein (2002) Phagosome maturation: aging gracefully. Biochem J 366: 689–704.
21.
Wright, H.L., H.S. McCarthy, J. Middleton, M.J. Marshall (2009) RANK, RANKL and osteoprotegerin in bone biology and disease. Curr Rev Musculoskelet Med 2: 56–64.
© 2011 S. Karger AG, Basel
2011
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.