This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Asou, Y. Articles by Noda, M. Search for Related Content PubMed PubMed Citation Articles by Asou, Y. Articles by Noda, M.

Osteopontin Facilitates Angiogenesis, Accumulation of Osteoclasts, and Resorption in Ectopic Bone¹

Department of Molecular Pharmacology, Medical Research Institute (Y.A., H.Y., K.T., A.N., M.N.), and Department of Orthopedic Surgery (K.S.), Tokyo Medical and Dental University, Tokyo 101-0062, Japan; and Department of Cell Biology and Neuroscience, Rutgers University (S.R.R., D.T.D.), Piscataway, New Jersey 08854

Address all correspondence and requests for reprints to: Masaki Noda, M.D., Ph.D., Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 2–3-10 Kanda, Surugadai Chiyoda-ku, Tokyo, Japan. E-mail: noda.mph{at}mri.tmd.ac.jp

Osteoclastic bone resorption requires a number of complex steps that are under the control of local regulatory molecules. Osteopontin is expressed in osteoclasts and is also present in bone matrix; however, its biological function has not been fully understood. To elucidate the role of osteopontin in the process of osteoclastic bone resorption, we conducted ectopic bone implantation experiments using wild-type and osteopontin knockout mouse. In the wild-type group, bone discs from calvariae implanted ectopically in muscle were resorbed, and their mass was reduced by 25% within 4 weeks. In contrast, the mass of the bone discs from calvariae of osteopontin knockout mice was reduced by only 5% when implanted in osteopontin knockout mice. Histological analyses indicated that the number of osteoclasts associated with the implanted bones was reduced in the osteopontin knockout mice. As osteopontin deficiency does not suppress osteoclastogenesis per se, we further examined vascularization immunohistologically and found that the number of vessels containing CD31-positive endothelial cells around the bone discs implanted in muscle was reduced in the osteopontin knockout mice. Furthermore, sc implantation assays indicated that the length and branching points of the newly formed vasculatures associated with the bone discs were also reduced in the absence of osteopontin. In this assay, tartrate-resistant acid phosphatase-positive area of the bone discs was also reduced in the osteopontin knockout mice, indicating further the link between the osteopontin-dependent vascularization and osteoclast accumulation. The bone resorption defect could be rescued by topical administration of recombinant osteopontin to the bones implanted in muscle. These observations indicate that osteopontin is required for efficient vascularization by the hemangiogenic endothelial cells and subsequent osteoclastic resorption of bones.

This article has been cited by other articles:

				L. Lam Shang Leen, C. Filipe, A. Billon, B. Garmy-Susini, S. Jalvy, F. Robbesyn, D. Daret, C. Allieres, S. R. Rittling, N. Werner, et al. Estrogen-Stimulated Endothelial Repair Requires Osteopontin Arterioscler. Thromb. Vasc. Biol., December 1, 2008; 28(12): 2131 - 2136. [Abstract] [Full Text] [PDF]

				J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden Migratory neighbors and distant invaders: tumor-associated niche cells Genes & Dev., March 1, 2008; 22(5): 559 - 574. [Abstract] [Full Text] [PDF]

				M. Ishijima, K. Tsuji, S. R Rittling, T. Yamashita, H. Kurosawa, D. T Denhardt, A. Nifuji, Y. Ezura, and M. Noda Osteopontin is required for mechanical stress-dependent signals to bone marrow cells J. Endocrinol., May 1, 2007; 193(2): 235 - 243. [Abstract] [Full Text] [PDF]

				M. Kolanczyk, N. Kossler, J. Kuhnisch, L. Lavitas, S. Stricker, U. Wilkening, I. Manjubala, P. Fratzl, R. Sporle, B. G. Herrmann, et al. Multiple roles for neurofibromin in skeletal development and growth Hum. Mol. Genet., April 15, 2007; 16(8): 874 - 886. [Abstract] [Full Text] [PDF]

				Y. Tanaka, M. Abe, M. Hiasa, A. Oda, H. Amou, A. Nakano, K. Takeuchi, K. Kitazoe, S. Kido, D. Inoue, et al. Myeloma Cell-Osteoclast Interaction Enhances Angiogenesis Together with Bone Resorption: A Role for Vascular Endothelial Cell Growth Factor and Osteopontin Clin. Cancer Res., February 1, 2007; 13(3): 816 - 823. [Abstract] [Full Text] [PDF]

				R. C. Johnson, J. A. Leopold, and J. Loscalzo Vascular Calcification: Pathobiological Mechanisms and Clinical Implications Circ. Res., November 10, 2006; 99(10): 1044 - 1059. [Abstract] [Full Text] [PDF]

				A. Naldini, D. Leali, A. Pucci, E. Morena, F. Carraro, B. Nico, D. Ribatti, and M. Presta Cutting Edge: IL-1beta Mediates the Proangiogenic Activity of Osteopontin-Activated Human Monocytes J. Immunol., October 1, 2006; 177(7): 4267 - 4270. [Abstract] [Full Text] [PDF]

				Q. Shen and S. Christakos The Vitamin D Receptor, Runx2, and the Notch Signaling Pathway Cooperate in the Transcriptional Regulation of Osteopontin J. Biol. Chem., December 9, 2005; 280(49): 40589 - 40598. [Abstract] [Full Text] [PDF]

				S. K. Nilsson, H. M. Johnston, G. A. Whitty, B. Williams, R. J. Webb, D. T. Denhardt, I. Bertoncello, L. J. Bendall, P. J. Simmons, and D. N. Haylock Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells Blood, August 15, 2005; 106(4): 1232 - 1239. [Abstract] [Full Text] [PDF]

				M. E. Davis, P. C.H. Hsieh, A. J. Grodzinsky, and R. T. Lee Custom Design of the Cardiac Microenvironment With Biomaterials Circ. Res., July 8, 2005; 97(1): 8 - 15. [Abstract] [Full Text] [PDF]

				G.D.M. Collett and A.E. Canfield Angiogenesis and Pericytes in the Initiation of Ectopic Calcification Circ. Res., May 13, 2005; 96(9): 930 - 938. [Abstract] [Full Text] [PDF]

				M.-A. Renault, S. Jalvy, M. Potier, I. Belloc, E. Genot, L. V. Dekker, C. Desgranges, and A.-P. Gadeau UTP Induces Osteopontin Expression through a Coordinate Action of NF{kappa}B, Activator Protein-1, and Upstream Stimulatory Factor in Arterial Smooth Muscle Cells J. Biol. Chem., January 28, 2005; 280(4): 2708 - 2713. [Abstract] [Full Text] [PDF]

				M. Abe, K. Hiura, J. Wilde, A. Shioyasono, K. Moriyama, T. Hashimoto, S. Kido, T. Oshima, H. Shibata, S. Ozaki, et al. Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion Blood, October 15, 2004; 104(8): 2484 - 2491. [Abstract] [Full Text] [PDF]

				H. Kojima, T. Uede, and T. Uemura In Vitro and In Vivo Effects of the Overexpression of Osteopontin on Osteoblast Differentiation Using a Recombinant Adenoviral Vector J. Biochem., September 1, 2004; 136(3): 377 - 386. [Abstract] [Full Text] [PDF]

				M. Gattorno, A. Gregorio, F. Ferlito, V. Gerloni, A. Parafioriti, E. Felici, E. Sala, C. Gambini, P. Picco, and A. Martini Synovial expression of osteopontin correlates with angiogenesis in juvenile idiopathic arthritis Rheumatology, September 1, 2004; 43(9): 1091 - 1096. [Abstract] [Full Text] [PDF]

				T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]

				M. Abedin, Y. Tintut, and L. L. Demer Vascular Calcification: Mechanisms and Clinical Ramifications Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1161 - 1170. [Abstract] [Full Text] [PDF]

				D. O'Gradaigh and J. E. Compston T-cell involvement in osteoclast biology: implications for rheumatoid bone erosion Rheumatology, February 1, 2004; 43(2): 122 - 130. [Full Text] [PDF]

				A. Vacca, R. Ria, F. Semeraro, F. Merchionne, M. Coluccia, A. Boccarelli, C. Scavelli, B. Nico, A. Gernone, F. Battelli, et al. Endothelial cells in the bone marrow of patients with multiple myeloma Blood, November 1, 2003; 102(9): 3340 - 3348. [Abstract] [Full Text] [PDF]

				D. Leali, P. Dell'Era, H. Stabile, B. Sennino, A. F. Chambers, A. Naldini, S. Sozzani, B. Nico, D. Ribatti, and M. Presta Osteopontin (Eta-1) and Fibroblast Growth Factor-2 Cross-Talk in Angiogenesis J. Immunol., July 15, 2003; 171(2): 1085 - 1093. [Abstract] [Full Text] [PDF]

				A. Hirata, S. Masuda, T. Tamura, K. Kai, K. Ojima, A. Fukase, K. Motoyoshi, K. Kamakura, Y. Miyagoe-Suzuki, and S.'i. Takeda Expression Profiling of Cytokines and Related Genes in Regenerating Skeletal Muscle after Cardiotoxin Injection: A Role for Osteopontin Am. J. Pathol., July 1, 2003; 163(1): 203 - 215. [Abstract] [Full Text] [PDF]

				D. L. Myers, K. J. Harmon, V. Lindner, and L. Liaw Alterations of Arterial Physiology in Osteopontin-Null Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2003; 23(6): 1021 - 1028. [Abstract] [Full Text] [PDF]

				M. Y. Speer, M. D. McKee, R. E. Guldberg, L. Liaw, H.-Y. Yang, E. Tung, G. Karsenty, and C. M. Giachelli Inactivation of the Osteopontin Gene Enhances Vascular Calcification of Matrix Gla Protein-deficient Mice: Evidence for Osteopontin as an Inducible Inhibitor of Vascular Calcification In Vivo J. Exp. Med., October 21, 2002; 196(8): 1047 - 1055. [Abstract] [Full Text] [PDF]

				K. Yumoto, M. Ishijima, S. R. Rittling, K. Tsuji, Y. Tsuchiya, S. Kon, A. Nifuji, T. Uede, D. T. Denhardt, and M. Noda Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice PNAS, April 2, 2002; 99(7): 4556 - 4561. [Abstract] [Full Text] [PDF]

				H Bull, P G Murray, D Thomas, A M Fraser, and P N Nelson Acid phosphatases Mol. Pathol., April 1, 2002; 55(2): 65 - 72. [Abstract] [Full Text] [PDF]

				W. Yang, S. J. Hyllner, and S. Christakos Interrelationship between signal transduction pathways and 1,25(OH)2D3 in UMR106 osteoblastic cells Am J Physiol Endocrinol Metab, July 1, 2001; 281(1): E162 - E170. [Abstract] [Full Text] [PDF]