Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease
Open accessAbstract
The platelet glycoprotein Ib-IX receptor binds surface-bound von Willebrand factor and supports platelet adhesion to damaged vascular surfaces. A limited number of mutations within the glycoprotein Ib-IX complex have been described that permit a structurally altered receptor to interact with soluble von Willebrand factor, and this is the molecular basis of platelet-type von Willebrand disease. We have developed and characterized a mouse model of platelet-type von Willebrand disease (G233V) and have confirmed a platelet phenotype mimicking the human disorder. The mice have a dramatic increase in splenic megakaryocytes and splenomegaly. Recent studies have demonstrated that hematopoetic cells can influence the differentiation of osteogenic cells. Thus, we examined the skeletal phenotype of mice expressing the G233V variant complex. At 6 months of age, G233V mice exhibit a high bone mass phenotype with an approximate doubling of trabecular bone volume in both the tibia and femur. Serum measures of bone resorption were significantly decreased in G233V animals. With decreased bone resorption, cortical thickness was increased, medullary area decreased, and consequently, the mechanical strength of the femur was significantly increased. Using ex vivo bone marrow cultures, osteoclast-specific staining in the G233V mutant marrow was diminished, whereas osteoblastogenesis was unaffected. These studies provide new insights into the relationship between the regulation of megakaryocytopoiesis and bone mass.
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Transgenic mice expressing a mutant form of VWF corresponding to platelet-type von Willebrand disease exhibit a high bone mass phenotype.
“Although mice lacking VWF have been reported to have normal bone density (36), transgenic mice expressing a mutant form of the protein corresponding to that seen in patients with platelet-type von Willebrand disease exhibit a high bone mass phenotype (37).”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [37]
The paper’s ‘High Bone Mass Phenotype as a Consequence of the G233V Mutation’ section reports increased bone volume in the transgenic mice. But the introductory passage identifies the expressed mutation as G233V in the platelet GP Ibα receptor, not in VWF. The bone-mass finding is supported; the mutant protein is misidentified. (LLM, conf=0.90)
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PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,015 · see citing works
Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258 · see citing works
BIOCHEMISTRY AND GENETICS OF VON WILLEBRAND FACTOR
Sadler, J. E. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.395 · Cited by 1,369 · see citing works
Hildebrand, T., Laib, A., Müller, R., Dequeker, J., & Ruegsegger, P. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.7.1167 · Cited by 1,303 · see citing works
Structures of Glycoprotein Ibα and Its Complex with von Willebrand Factor A1 Domain
Huizinga, E. G., Tsuji, S., Romijn, R. A., Schiphorst, M. E., de Groot, P. G., Sixma, J. J., & Gros, P. (2002) · Science · doi:10.1126/science.107355 · Cited by 545 · see citing works
Inducible secretion of large, biologically potent von Willebrand factor multimers
Sporn, L. A., Marder, V. J., & Wagner, D. D. (1986) · Cell · doi:10.1016/0092-8674(86)90735-x · Cited by 456 · see citing works
Bone Is a Target for the Antidiabetic Compound Rosiglitazone
Rzońca, S., Suva, L. J., Gaddy, D., Montague, D. C., & Lecka‐Czernik, B. (2003) · Endocrinology · doi:10.1210/en.2003-0746 · Cited by 455 · see citing works
Self-citationIshida, N., Hayashi, K., Hoshijima, M., Ogawa, T., Koga, S., Miyatake, Y., Kumegawa, M., Kimura, T., & Takeya, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205063200 · Cited by 377 · see citing works
Consequences of GATA-1 Deficiency in Megakaryocytes and Platelets
Vyas, P., Ault, K., Jackson, C. W., Orkin, S. H., & Shivdasani, R. A. (1999) · Blood · doi:10.1182/blood.v93.9.2867.409k24_2867_2875 · Cited by 362 · see citing works
Consequences of GATA-1 Deficiency in Megakaryocytes and Platelets
Vyas, P., Ault, K. A., Jackson, C. W., Orkin, S. H., & Shivdasani, R. A. (1999) · Blood · doi:10.1182/blood.v93.9.2867 · Cited by 357 · see citing works
Kaneko, H., Arakawa, T., Mano, H., Kaneda, T., Ogasawara, A., Nakagawa, M., Toyama, Y., Yabe, Y., Kumegawa, M., & Hakeda, Y. (2000) · Bone · doi:10.1016/s8756-3282(00)00358-6 · Cited by 347 · see citing works
Rosiglitazone Induces Decreases in Bone Mass and Strength that Are Reminiscent of Aged Bone
Lazarenko, O. P., Rzońca, S., Hogue, W. R., Swain, F. L., Suva, L. J., & Lecka‐Czernik, B. (2007) · Endocrinology · doi:10.1210/en.2006-1587 · Cited by 302 · see citing works
Self-citationNichols, W. C., & Ginsburg, D. B. (1997) · Medicine · doi:10.1097/00005792-199701000-00001 · Cited by 296 · see citing works
Loscalzo, J., & Schafer, A. I. (2002) · Cited by 291 · see citing works
Generation and rescue of a murine model of platelet dysfunction: the Bernard-Soulier syndrome.
Ware, J., Russell, S., & Ruggeri, Z. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.050582097 · Cited by 290 · see citing works
Self-citationKwaan, H. C. (2003) · JAMA · doi:10.1001/jama.289.22.3014-b · Cited by 240 · see citing works
Rogers, A., & Eastell, R. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0794 · Cited by 215 · see citing works
Bendre, M. S., Gaddy-Kurten, D., Mon-Foote, T., Akel, N. S., Skinner, R. A., Nicholas, R. W., & Suva, L. J. (2002) · PubMed · Cited by 212 · see citing works
Self-citationBone Morphogenetic Proteins in Bone Stimulate Osteoclasts and Osteoblasts During Bone Development
Okamoto, M., Murai, J., Yoshikawa, H., & Tsumaki, N. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060411 · Cited by 212 · see citing works
Andrews, R. K., Gardiner, E. E., Shen, Y., Whisstock, J. C., & Berndt, M. C. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00280-7 · Cited by 209 · see citing works
Yan, X., Lacey, D. L., Hill, D., Chen, Y., Fletcher, F., Hawley, R. G., & Ik, M. (1996) · Blood · doi:10.1182/blood.v88.2.402.bloodjournal882402 · Cited by 202 · see citing works
Platelet-type von Willebrand's disease: characterization of a new bleeding disorder
Miller, J., & Castella, A. (1982) · Blood · doi:10.1182/blood.v60.3.790.790 · Cited by 202 · see citing works
Cappellen, D., Luong-Nguyen, N.-H., Bongiovanni, S., Grenet, O., Wanke, C., & Šuša, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200434200 · Cited by 184 · see citing works
López, J. A., Leung, B., Reynolds, C. C., Li, C. Q., & Fox, J. E. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42354-x · Cited by 175 · see citing works
Miller, J. L., Cunningham, D., Lyle, V. A., & Finch, C. N. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.11.4761 · Cited by 156 · see citing works
Pattern of gene expression following rat tibial marrow ablation
Suva, L. J., Seedor, G., Endo, N., Quartuccio, H. A., Thompson, D. D., Bab, I., & Rodan, G. A. (1993) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650080315 · Cited by 149 · see citing works
Self-citationGaddy-Kurten, D., Coker, J., Abe, E., Jilka, R. L., & Manolagas, S. C. (2002) · Endocrinology · doi:10.1210/endo.143.1.8580 · Cited by 145 · see citing works
Kacena, M. A., Shivdasani, R. A., Wilson, K. M., Xi, Y., Troiano, N. W., Nazarian, A., Gundberg, C. M., Bouxsein, M., Lorenzo, J. A., & Horowitz, M. C. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301254 · Cited by 136 · see citing works
Bagi, C. M., Hanson, N., Andresen, C. J., Pero, R. W., Lariviere, R., Turner, C. H., & Laib, A. (2005) · Bone · doi:10.1016/j.bone.2005.07.028 · Cited by 135 · see citing works
Scott, J. P., Montgomery, R. R., & Retzinger, G. S. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)92954-6 · Cited by 133 · see citing works
Budde, U., Schneppenheim, R., Plendl, H., Dent, J., Ruggeri, Z. M., & Zimmerman, T. S. (1990) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1645215 · Cited by 115 · see citing works
Self-citationA reciprocal regulatory interaction between megakaryocytes, bone cells, and hematopoietic stem cells
Kacena, M. A., Gundberg, C. M., & Horowitz, M. C. (2006) · Bone · doi:10.1016/j.bone.2006.05.019 · Cited by 114 · see citing works
Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength
Perrien, D. S., Akel, N. S., Edwards, P. K., Carver, A. A., Bendre, M. S., Swain, F. L., Skinner, R. A., Hogue, W. R., Nicks, K. M., Pierson, T. M., et al. (2006) · Endocrinology · doi:10.1210/en.2006-0848 · Cited by 111 · see citing works
Self-citationLocalization of bone morphogenetic proteins (BMPs)-2, -4, and -6 within megakaryocytes and platelets
Sipe, J. B., Zhang, J., Waits, C., Skikne, B., Garimella, R., & Anderson, H. C. (2004) · Bone · doi:10.1016/j.bone.2004.08.020 · Cited by 101 · see citing works
Miller, J. L., Kupinski, J. M., Castella, A., & Ruggeri, Z. M. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111112 · Cited by 100 · see citing works
Hashimoto, Y., & Ware, J. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.24532 · Cited by 98 · see citing works
Self-citationOthman, M., Notley, C. R. P., Lavender, F. L., White, H., Byrne, C. D., Lillicrap, D., & O’Shaughnessy, D. (2005) · Blood · doi:10.1182/blood-2002-09-2942 · Cited by 88 · see citing works
Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia
Nurden, P., Debili, N., Vainchenker, W., Bobe, R., Bredoux, R., Corvazier, E., Combrié, R., Fressinaud, É., Meyer, D., Nurden, A. T., et al. (2006) · Blood · doi:10.1182/blood-2006-03-009449 · Cited by 87 · see citing works
Megakaryocyte-mediated inhibition of osteoclast development
Kacena, M. A., Nelson, T., Clough, M. E., Lee, S., Lorenzo, J. A., Gundberg, C. M., & Horowitz, M. C. (2006) · Bone · doi:10.1016/j.bone.2006.05.004 · Cited by 83 · see citing works
Bone morphogenetic proteins 5 and 6 stimulate osteoclast generation
Wutzl, A., Brozek, W., Lernbass, I., Rauner, M., Hofbauer, G., Schopper, C., Watzinger, F., Peterlik, M., & Pietschmann, P. (2005) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30615 · Cited by 74 · see citing works
Platelet-type von Willebrand Disease
Miller, J. L. (1996) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1650385 · Cited by 71 · see citing works
Aging alters the skeletal response to disuse in the rat
Perrien, D. S., Akel, N. S., Dupont‐Versteegden, E. E., Skinner, R. A., Siegel, E. R., Suva, L. J., & Gaddy, D. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00302.2006 · Cited by 68 · see citing works
Self-citationWare, J. L., Dent, J. A., Azuma, H., Sugimoto, M., Kyrle, P. A., Yoshioka, A., & Ruggeri, Z. M. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.7.2946 · Cited by 67 · see citing works
Self-citationMegakaryocytes modulate osteoblast synthesis of type-l collagen, osteoprotegerin, and RANKL
BORD, S., FRITH, E., IRELAND, D., SCOTT, M., CRAIG, J., & COMPSTON, J. (2005) · Bone · doi:10.1016/j.bone.2004.12.006 · Cited by 63 · see citing works
Zieger, B., Hashimoto, Y., & Ware, J. L. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119188 · Cited by 63 · see citing works
Self-citationDysfunctional platelet membrane receptors: from humans to mice
Ware, J. L. (2004) · Thrombosis and Haemostasis · doi:10.1160/th04-05-0308 · Cited by 62 · see citing works
Self-citationOsteoclast formation and bone resorption are inhibited by megakaryocytes
Beeton, C. A., Bord, S., Ireland, D., & Compston, J. E. (2006) · Bone · doi:10.1016/j.bone.2006.06.004 · Cited by 61 · see citing works
Kacena, M. A., Gundberg, C. M., Nelson, T., & Horowitz, M. C. (2005) · Bone · doi:10.1016/j.bone.2004.09.024 · Cited by 58 · see citing works
Molecular Analyses of the Platelet Glycoprotein Ib-IX-V Receptor
Ware, J. L. (1998) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614928 · Cited by 55 · see citing works
Self-citationMatsubara, Y., Murata, M., Sugita, K., & Ikeda, Y. (2003) · Journal of Thrombosis and Haemostasis · doi:10.1046/j.1538-7836.2003.00369.x · Cited by 49 · see citing works
Expression of human platelet glycoprotein Ib alpha in transgenic mice.
Ware, J. L., Russell, S., Marchese, P., & Ruggeri, Z. M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53105-7 · Cited by 43 · see citing works
Self-citationDecalcified Bone: Twenty Years of Successful Specimen Management
Skinner, R. A., Hickmon, S. G., Lumpkin, C. K., Aronson, J., & Nicholas, R. W. (1997) · Journal of Histotechnology · doi:10.1179/his.1997.20.3.267 · Cited by 43 · see citing works
Self-citationInsights into von Willebrand factor proteolysis: clinical implications
Bowen, D. J., & Collins, P. W. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06096.x · Cited by 43 · see citing works
Murata, M., Russell, S., Ruggeri, Z. M., & Ware, J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116438 · Cited by 36 · see citing works
Self-citationMoriki, T., Murata, M., Kitaguchi, T., Anbo, H., Handa, M., Watanabe, K., Takahashi, H., & Ikeda, Y. (1997) · Blood · doi:10.1182/blood.v90.2.698 · Cited by 36 · see citing works
Garimella, R., Kacena, M. A., Tague, S. E., Wang, J., Horowitz, M. C., & Anderson, H. C. (2007) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.6a7164.2007 · Cited by 31 · see citing works
In Vivo Expression of Murine Platelet Glycoprotein Ibα
Fujita, H., Hashimoto, Y., Russell, S., Zieger, B., & Ware, J. L. (1998) · Blood · doi:10.1182/blood.v92.2.488 · Cited by 29 · see citing works
Self-citationThe Role of Transcription Factor NF‐E2 in Megakaryocyte Maturation and Platelet Production
Shivdasani, R. A. (1996) · Stem Cells · doi:10.1002/stem.5530140714 · Cited by 20 · see citing works
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Research works printed but not linked: 3
- Andrews RK, Gardiner EE, Shen Y, Whisstock JC, Berndt MC: Gly- coprotein Ib-IX-V. Int J Biochem Cell Biol 2003, 35:1170 -1174
- Skinner R, Hickmon S, Lumpkin CJ, Aronson J, Nicholas R: Twenty years of successful specimen management. J Histotechnol 1997, 20:267-277
- Huizinga EG, Tsuji S, Romijn RA, Schiphorst ME, de Groot PG, Sixma JJ, Gros P: Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science 2002, 297:1176 -1179
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Suva, L. J., Washam, C. L., Nicholas, R. W., & Griffin, R. J. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.227 · Cited by 423 · see citing works
Self-citationMetastasis: new functional implications of platelets and megakaryocytes
Leblanc, R., & Peyruchaud, O. (2016) · Blood · doi:10.1182/blood-2016-01-636399 · Cited by 232 · see citing works
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Bryckaert, M., Rosa, J., Denis, C. V., & Lenting, P. J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1743-8 · Cited by 223 · see citing works
Mohammad, K. S., Chen, C. G., Balooch, G., Stebbins, E. G., McKenna, C. R., Davis, H., Niewolna, M., Peng, X., Nguyen, D. H., Ionova-Martin, S. S., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005275 · Cited by 179 · see citing works
Self-citationA reliable murine model of bone metastasis by injecting cancer cells through caudal arteries
Kuchimaru, T., Kataoka, N., Nakagawa, K., Isozaki, T., Miyabara, H., Minegishi, M., Kadonosono, T., & Kizaka‐Kondoh, S. (2018) · Nature Communications · doi:10.1038/s41467-018-05366-3 · Cited by 144 · see citing works
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Nurden, A. T., & Nurden, P. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04274.x · Cited by 140 · see citing works
Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight
Lee, S.-J., Lehar, A., Meir, J. U., Koch, C., Morgan, A., Warren, L. E., Rydzik, R., Youngstrom, D. W., Chandok, H., George, J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2014716117 · Cited by 115 · see citing works
“Although mice lacking VWF have been reported to have normal bone density (36), transgenic mice expressing a mutant form of the protein corresponding to that seen in patients with platelet-type von Willebrand disease exhibit a high bone mass phenotype (37).”
The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling
Su, X., Floyd, D. H., Hughes, A., Xiang, J., Schneider, J. G., Uluçkan, Ö., Heller, E., Deng, H., Zou, W., Craft, C. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci38576 · Cited by 104 · see citing works
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Malara, A., Abbonante, V., Buduo, C. A. D., Tozzi, L., Currao, M., & Balduini, A. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1813-y · Cited by 92 · see citing works
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Baud’huin, M., Duplomb, L., Télétchéa, S., Charrier, C., Maillasson, M., Fouassier, M., & Heymann, D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.030312 · Cited by 89 · see citing works
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Self-citationJohnsson, M., Jonsson, K. B., Andersson, L., Jensen, P., & Wright, D. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005250 · Cited by 58 · see citing works
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Jia, D., Gaddy, D., Suva, L. J., & Corry, P. M. (2011) · Radiation Research · doi:10.1667/rr2505.1 · Cited by 57 · see citing works
Self-citationHeard, M. E., Besio, R., Weis, M., Rai, J., Hudson, D. M., Dimori, M., Zimmerman, S. M., Kamykowski, J. A., Hogue, W. R., Swain, F. L., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006002 · Cited by 57 · see citing works
Self-citationKaur, H., Emsley, J., & Othman, M. (2013) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0033-1353442 · Cited by 56 · see citing works
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Self-citationOthman, M. (2011) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0031-1281030 · Cited by 53 · see citing works
Lemieux, J. M., Horowitz, M. C., & Kacena, M. A. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22468 · Cited by 52 · see citing works
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Self-citationAdam, F., Casari, C., Prévost, N., Kauskot, A., Loubière, C., Legendre, P., Repérant, C., Baruch, D., Rosa, J., Bryckaert, M., et al. (2016) · Scientific Reports · doi:10.1038/srep26306 · Cited by 33 · see citing works
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Cheng, Y., Hooker, R. A., Nguyen, K., Gerard-O’Riley, R. L., Waning, D. L., Chitteti, B. R., Meijome, T. E., Chua, H. L., Plett, A., Orschell, C. M., et al. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1876 · Cited by 28 · see citing works
Kumar, R., & Kahr, W. H. A. (2013) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2013.02.004 · Cited by 27 · see citing works
Mercer, K. E., Sims, C. R., Yang, C. S., Wynne, R. A., Moutos, C. P., Hogue, W. R., Lumpkin, C. K., Suva, L. J., Chen, J., Badger, T. M., et al. (2013) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12305 · Cited by 25 · see citing works
Self-citationInhibin A enhances bone formation during distraction osteogenesis
Perrien, D. S., Nicks, K. M., Liu, L., Akel, N. S., Bacon, A. W., Skinner, R. A., Swain, F. L., Aronson, J., Suva, L. J., & Gaddy, D. (2011) · Journal of Orthopaedic Research® · doi:10.1002/jor.21501 · Cited by 24 · see citing works
Self-citationMegakaryocyte Diversity in Ontogeny, Functions and Cell-Cell Interactions
Khatib-Massalha, E., & Méndez-Ferrer, S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.840044 · Cited by 24 · see citing works
Alund, A. W., Mercer, K. E., Pulliam, C. F., Suva, L. J., Chen, J., Badger, T. M., & Ronis, M. J. J. (2016) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13284 · Cited by 23 · see citing works
Self-citationHematopoietic Cell Regulation of Osteoblast Proliferation and Differentiation
Bethel, M., Srour, E. F., & Kacena, M. A. (2011) · Current Osteoporosis Reports · doi:10.1007/s11914-011-0048-1 · Cited by 22 · see citing works
Kamalakar, A., Washam, C. L., Akel, N. S., Allen, B. J., Williams, D. K., Swain, F. L., Leitzel, K. E., Lipton, A., Gaddy, D., & Suva, L. J. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3142 · Cited by 22 · see citing works
Self-citationRegulation of bone metabolism by megakaryocytes in a paracrine manner
Lee, Y., Kwak, M. K., Moon, S.-A., Choi, Y. J., Baek, J. E., Park, S. Y., Kim, B., Lee, S. H., & Koh, J. (2020) · Scientific Reports · doi:10.1038/s41598-020-59250-6 · Cited by 22 · see citing works
Robinson, J. W., Blixt, N. C., Norton, A., Mansky, K. C., Ye, Z., Aparicio, C., Wagner, B. M., Benton, A. M., Warren, G. L., Khosla, S., et al. (2020) · Bone · doi:10.1016/j.bone.2020.115320 · Cited by 22 · see citing works
Self-citationA Novel Role for Thrombopoietin in Regulating Osteoclast Development in Humans and Mice
Bethel, M., Barnes, C. L. T., Taylor, A. F., Cheng, Y., Chitteti, B. R., Horowitz, M. C., Bruzzaniti, A., Srour, E. F., & Kacena, M. A. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.24943 · Cited by 21 · see citing works
Platelet-type von Willebrand disease update: the disease, the molecule and the animal model
Othman, M., López, J. A., & Ware, J. L. (2011) · Expert Review of Hematology · doi:10.1586/ehm.11.45 · Cited by 20 · see citing works
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Leblanc, R., & Peyruchaud, O. (2016) · Journal of bone oncology · doi:10.1016/j.jbo.2016.02.007 · Cited by 20 · see citing works
GATA‐1 Deficiency Rescues Trabecular but not Cortical Bone in OPG Deficient Mice
Meijome, T. E., Hooker, R. A., Cheng, Y., Walker, W., Horowitz, M. C., Fuchs, R. K., & Kacena, M. A. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.24803 · Cited by 18 · see citing works
Watt, J. D., Alund, A. W., Pulliam, C. F., Mercer, K. E., Suva, L. J., Chen, J., & Ronis, M. J. J. (2018) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.117.247262 · Cited by 18 · see citing works
Self-citationRonis, M. J. J., Watt, J. D., Pulliam, C. F., Williams, A. E., Alund, A. W., Haque, E., Gadupudi, G. S., & Robertson, L. W. (2019) · Archives of Toxicology · doi:10.1007/s00204-019-02645-w · Cited by 18 · see citing works
Signaling Pathways Involved in Megakaryocyte‐Mediated Proliferation of Osteoblast Lineage Cells
Cheng, Y., Streicher, D. A., Waning, D. L., Chitteti, B. R., Gerard-O’Riley, R. L., Horowitz, M. C., Bidwell, J. P., Pavalko, F. M., Srour, E. F., Mayo, L. D., et al. (2014) · Journal of Cellular Physiology · doi:10.1002/jcp.24774 · Cited by 17 · see citing works
Kaur, H., Corscadden, K., Ware, J. L., & Othman, M. (2016) · Thrombosis and Haemostasis · doi:10.1160/th16-04-0317 · Cited by 17 · see citing works
Self-citationWilliams, D. K., Parham, S. G., Schryver, E. M., Akel, N. S., Shelton, R. S., Webber, J. S., Swain, F. L., Schmidt, J., Suva, L. J., & Gaddy, D. (2017) · JBMR Plus · doi:10.1002/jbm4.10025 · Cited by 16 · see citing works
Self-citationBury, L., Falcinelli, E., Mezzasoma, A. M., Guglielmini, G., Momi, S., & Gresele, P. (2021) · Haematologica · doi:10.3324/haematol.2021.278776 · Cited by 16 · see citing works
Platelets increase while serum reduces the differentiation and activity of osteoclasts in vitro
Agis, H., Schröckmair, S., Skorianz, C., Fischer, M. B., Watzek, G., & Gruber, R. (2013) · Journal of Orthopaedic Research® · doi:10.1002/jor.22386 · Cited by 16 · see citing works
Megakaryocyte-Bone Cell Interactions
Kacena, M. A., & Ciovacco, W. A. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-1050-9_4 · Cited by 16 · see citing works
Megakaryocytes promote osteoclastogenesis in aging
Kanagasabapathy, D., Blosser, R. J., Maupin, K. A., Hong, J. M., Alvarez, M. B., Ghosh, J., Mohamad, S., Aguilar‐Perez, A., Srour, E. F., Kacena, M. A., et al. (2020) · Aging · doi:10.18632/aging.103595 · Cited by 14 · see citing works
Low bone mass and impaired fracture healing in mouse models of Trisomy21 (Down syndrome)
Sherman, K. M., Williams, D. K., Welsh, C. A., Cooper, A., Falck, A. R., Huggins, S. S., Bokhari, R. S., Gaddy, D., McKelvey, K. D., Dawson, L., et al. (2022) · Bone · doi:10.1016/j.bone.2022.116471 · Cited by 13 · see citing works
Self-citationAlund, A. W., Mercer, K. E., Suva, L. J., Pulliam, C. F., Chen, J.-R., Badger, T. M., Remmen, H. V., & Ronis, M. J. J. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.233213 · Cited by 13 · see citing works
Self-citationWilliams, A. E., Watt, J. D., Robertson, L. W., Gadupudi, G. S., Osborn, M. L., Soares, M. J., Iqbal, K., Pedersen, K. B., Shankar, K., Littleton, S., et al. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa030 · Cited by 13 · see citing works
Self-citationKarnik, S. J., Nazzal, M. K., Kacena, M. A., & Bruzzaniti, A. (2023) · Calcified Tissue International · doi:10.1007/s00223-023-01095-y · Cited by 12 · see citing works
Alanne, M. H., Siljamäki, E., Peltonen, S. A., Väänänen, K., Windle, J. J., Parada, L. F., Määttä, J. A., & Peltonen, J. T. K. (2012) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24088 · Cited by 11 · see citing works
Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype
Olivos, D. J., Alvarez, M. B., Cheng, Y., Hooker, R. A., Ciovacco, W. A., Bethel, M., McGough, H., Yim, C., Chitteti, B. R., Eleniste, P. P., et al. (2017) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25874 · Cited by 11 · see citing works
Stavnichuk, M., & Komarova, S. V. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00328.2021 · Cited by 10 · see citing works
Kanaji, S., Morodomi, Y., Weiler-Guettler, H., Zarpellon, A., Montgomery, R. R., Ruggeri, Z. M., & Kanaji, T. (2022) · Haematologica · doi:10.3324/haematol.2021.280561 · Cited by 8 · see citing works
Self-citationRonis, M. J. J., Mercer, K. E., Suva, L. J., Vantrease, J., Ferguson, M. E., Hogue, W. R., Sharma, N., Cleves, M. A., Blackburn, M. L., & Badger, T. M. (2014) · Alcohol · doi:10.1016/j.alcohol.2013.12.005 · Cited by 8 · see citing works
Self-citationKazmirchuk, T. D. D., Wang, J., Bury, L., Falcinelli, E., Bradbury-Jost, C., Koziar, A., Al‐gafari, M., Takallou, S., Willmore, W. G., Dehne, F., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025017674 · Cited by 6 · see citing works
Thrombopoietic agents enhance bone healing in mice, rats, and pigs
Childress, P., Nielsen, J. J., Bemenderfer, T. B., Dadwal, U. C., Chakraborty, N., Harris, J. S., Bethel, M., Alvarez, M. B., Tucker, A., Wessel, A. R., et al. (2024) · Journal of Bone and Mineral Research · doi:10.1093/jbmr/zjae191 · Cited by 5 · see citing works
Denys, A., Norman, A. R., Perrien, D. S., Suva, L. J., Simon, L., McDaniel, L. S., Ferguson, T. F., Pedersen, K. B., Welsh, D. A., Molina, P. E., et al. (2022) · JBMR Plus · doi:10.1002/jbm4.10703 · Cited by 5 · see citing works
Self-citationPapadantonakis, N., & Ravid, K. (2009) · Springer eBooks · doi:10.1007/978-0-387-85816-6_5 · Cited by 4 · see citing works
Clemetson, K. J. (2010) · doi:10.1002/9781444318531.ch20 · Cited by 3 · see citing works
Karagianni, A., Matsuura, S., Gerstenfeld, L. C., & Ravid, K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.929498 · Cited by 2 · see citing works
Imaging bone blood perfusion: Not just going with the flow
Suva, L. J., & Gaddy, D. (2013) · Bone · doi:10.1016/j.bone.2013.04.014
Self-citationMegakaryoctye-Bone Cell Interactions: The Role of Gap Junctions, Maturation, and Longevity
Ciovacca, W. A. (2009) · Europe PMC (PubMed Central)
Clemetson, K. J. (2019) · doi:10.1002/9781119252863.ch19
Ware, J. L., & Corken, A. L. (2015) · Atherosclerosis · doi:10.1002/9781118828533.ch15
Self-citationClemetson, K. J. (2024) · doi:10.1002/9781394180486.ch18
Alkhatib, A. R., Elshimy, Y., Atassi, B., & Mohammad, K. S. (2026) · Biomedicines · doi:10.3390/biomedicines14010161
Designing the Future of Hemostasis
Kazmirchuk, T. D. D., Wang, J., Corbette, J., Hammad, Z. A. A., Othman, M., & Golshani, A. (2026) · Seminars in Thrombosis and Hemostasis · doi:10.1055/a-2885-4368
Platelet Type Von Willebrand Disease – Diagnostic and Therapeutic Challenges
Wiedenhoefer, R., Boeckelmann, D., Glonnegger, H., Oldenburg, J., & Zieger, B. (2026) · Hämostaseologie · doi:10.1055/a-2940-6179
Aksornthong, S., Tiedemann, K., Welman, M., Mazharian, A., Lordkipanidzé, M., Senis, Y. A., & Komarova, S. V. (2026) · Bone Research · doi:10.1038/s41413-026-00575-9
- Authors
- Suva, L. J., Hartman, E., Dilley, J. D., Russell, S., Akel, N. S., Skinner, R. A., Hogue, W. R., Budde, U., Varughese, K. I., Kanaji, T., & Ware, J.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Kurume University (JP)
- Corresponding author
- Ware, Jerry
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 172
- Issue
- 2
- Pages
- 430-439
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2312362
- OpenAlex
- W2093228291
- Cited by
- 75
- References
- 58
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 5
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL50541)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- platelet-type von Willebrand disease, von Willebrand factor, mouse model, high bone mass, trabecular bone volume, bone resorption, osteoclasts, osteoblastogenesis, megakaryopoiesis, splenomegaly, bone strength
- MeSH terms
- Animals, Bleeding Time, Blood Platelet Disorders, Blood Platelets, Bone and Bones, Cell Differentiation, Disease Models, Animal, Flow Cytometry, Humans, Mice, Transgenic, Osteoclasts, Phenotype, Protein Binding, Splenomegaly, von Willebrand Factor, von Willebrand Diseases, Protein Structure, Secondary, Platelet Glycoprotein GPIb-IX Complex, Thrombopoiesis, Mice
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