Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production
Open accessAbstract
Osteopontin (OPN), a multifunctional secreted phosphoglycoprotein, plays diverse roles in bone biology, immune regulation, cell survival, inflammation, and cancer metastasis. Here we show its role in determining lymphocyte homeostasis and body mass in response to hindlimb unloading (HU), a model for evaluating effects of weightlessness on the musculoskeletal and other physiological systems. Using this stress model, we compared OPN(-/-) mice with OPN(+/+) mice subjected to HU for 3 days. Whereas OPN(+/+) mice suffered a marked reduction of body weight and significant spleen and thymus atrophy, OPN(-/-) mice exhibited minor weight loss and much less spleen and thymus atrophy. The HU-induced lymphoid organ atrophy was the result of dramatically diminished numbers, respectively, of T and B cells in the spleen and CD4(+)CD8(+) double-positive cells in the thymus of OPN(+/+) mice. Increased levels of corticosterone, which modulates lymphocyte activation responses and apoptosis during stress, were found only in OPN(+/+) mice. Apoptotic cell death was evident in the spleen and thymus of OPN(+/+) mice subjected to HU but not in OPN(-/-)mice. Importantly, lymphocytes from both OPN(+/+) and OPN(-/-) mice were equally sensitive to corticosteroid-induced apoptosis. These results reveal that OPN is required for enhanced corticosterone production, immune organ atrophy, and weight loss in mice subjected to HU.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Space flight alters immune responses, certain of which could lead to potentially detrimental pathology.
“Space flight has been shown to alter immune responses, certain of which could lead to potentially detrimental pathology.”
From Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections (2014) · cites this paper as [2]
We observed a significant increase in corticosterone levels for hindlimb suspension.
“We observed a significant increase in corticosterone levels for hindlimb suspension, which is in agreement with most studies of hindlimb suspension [2], [58], [61], [62].”
From Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections (2014) · cites this paper as [2]
Cites
Eta-1 (Osteopontin): An Early Component of Type-1 (Cell-Mediated) Immunity
Ashkar, S., Weber, G. F., Panoutsakopoulou, V., Sanchirico, M. E., Jansson, M., Zawaideh, S., Rittling, S. R., Denhardt, D. T., Glimcher, M. J., & Cantor, H. (2000) · Science · doi:10.1126/science.287.5454.860 · Cited by 1,125 · see citing works
Self-citationDenhardt, D. T., Noda, M., O'Regan, A. W., Pavlin, D., & Berman, J. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12980 · Cited by 1,060 · see citing works
Self-citationThe influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease
Chabas, D., Baranzini, S. E., Mitchell, D., Bernard, C. C. A., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M., Pedotti, R., et al. (2001) · Science · doi:10.1126/science.1062960 · Cited by 829 · see citing works
Self-citationEffects of stress on immune cell distribution. Dynamics and hormonal mechanisms.
Dhabhar, F. S., Miller, A. H., McEwen, B. S., & Spencer, R. L. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.10.5511 · Cited by 730 · see citing works
THE INFLUENCE OF THE PROINFLAMMATORY CYTOKINE, OSTEOPONTIN, ON AUTOIMMUNE DEMYELINATING DISEASE
Chabas, D., Baranzini, S. E., Mitchell, D. J., Bernard, C. C. A., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M. V., Pedotti, R., et al. (2002) · International Conference on Osteopontin and SIBLING Proteins · doi:10.1100/tsw.2002.326 · Cited by 729 · see citing works
Self-citationEnhancing versus suppressive effects of stress hormones on skin immune function
Dhabhar, F. S., & McEwen, B. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.3.1059 · Cited by 672 · see citing works
Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes
Shi, Y., Sahai, B. M., & Green, D. R. (1989) · Nature · doi:10.1038/339625a0 · Cited by 505 · see citing works
Self-citationNieman, D. C., & Pedersen, B. K. (1999) · Sports Medicine · doi:10.2165/00007256-199927020-00001 · Cited by 466 · see citing works
Rittling, S. R., Matsumoto, H., McKee, M. D., Nanci, A., An, X.-R., Novick, K. E., Kowalski, A. J., Noda, M., & Denhardt, D. T. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.7.1101 · Cited by 439 · see citing works
Self-citationStress-induced enhancement of antigen-specific cell-mediated immunity
Dhabhar, F. S., & McEwen, B. S. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.7.2608 · Cited by 419 · see citing works
Offner, H., Subramanian, S., Parker, S. M., Wang, C., Afentoulis, M. E., Lewis, A. D., Vandenbark, A. A., & Hurn, P. D. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.11.6523 · Cited by 412 · see citing works
Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption
Yoshitake, H., Rittling, S. R., Denhardt, D. T., & Noda, M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.8156 · Cited by 374 · see citing works
Self-citationStress System Activity, Innate and T Helper Cytokines, and Susceptibility to Immune‐Related Diseases
CALCAGNI, E., & Elenkov, I. J. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1351.006 · Cited by 364 · see citing works
Osteopontin: a key cytokine in cell‐mediated and granulomatous inflammation
O'Regan, A. W., & Berman, J. S. (2000) · International Journal of Experimental Pathology · doi:10.1046/j.1365-2613.2000.00163.x · Cited by 357 · see citing works
Hur, E.-M., Youssef, S., Haws, M., Zhang, S. Y., Sobel, R. A., & Steinman, L. (2007) · Nature Immunology · doi:10.1038/ni1415 · Cited by 342 · see citing works
Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases.
Diao, H., Kon, S., Iwabuchi, K., Kimura, C., Morimoto, J., Ito, D., Segawa, T., Maeda, M., Hamuro, J., Nakayama, T., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.08.012 · Cited by 226 · see citing works
Self-citationYumoto, K., Ishijima, M., Rittling, S. R., Tsuji, K., Tsuchiya, Y. S., Kon, S., Nifuji, A., Uede, T., Denhardt, D. T., & Noda, M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052523599 · Cited by 208 · see citing works
Self-citationHwang, S. M., Lopez, C. A., Heck, D. E., Gardner, C. R., Laskin, D. L., Laskin, J. D., & Denhardt, D. T. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42407-0 · Cited by 176 · see citing works
Self-citationChronic Restraint Stress Promotes Lymphocyte Apoptosis by Modulating Cd95 Expression
Yin, D., Tuthill, D. P., Mufson, R. A., & Shi, Y. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.8.1423 · Cited by 174 · see citing works
Self-citationRenkl, A. C., Wussler, J., Ahrens, T., Thoma, K., Kon, S., Uede, T., Martin, S. F., Simon, J. C., & Weiss, J. M. (2005) · Blood · doi:10.1182/blood-2004-08-3228 · Cited by 173 · see citing works
T-bet-dependent expression of osteopontin contributes to T cell polarization.
Shinohara, M. L., Jansson, M., Hwang, E., Werneck, M. B. F., Glimcher, L., & Cantor, H. (2005) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0508666102 · Cited by 167 · see citing works
Stress, Leukocyte Trafficking, and the Augmentation of Skin Immune Function
Dhabhar, F. S. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb03151.x · Cited by 166 · see citing works
The role of osteopontin in lung disease.
O'Regan, A. (2003) · Cytokine & growth factor reviews · doi:10.1016/s1359-6101(03)00055-8 · Cited by 160 · see citing works
Stress-induced enhancement of skin immune function: A role for γ interferon
Dhabhar, F. S., Satoskar, A. R., Bluethmann, H., David, J. R., & McEwen, B. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050569397 · Cited by 156 · see citing works
Stress as an endogenous adjuvant: augmentation of the immunization phase of cell-mediated immunity
Viswanathan, K., Daugherty, C., & Dhabhar, F. S. (2005) · International Immunology · doi:10.1093/intimm/dxh286 · Cited by 138 · see citing works
Maetzler, W., Berg, D., Schalamberidze, N., Melms, A., Schott, K., Mueller, J. C., Liaw, L., Gasser, T., & Nitsch, C. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.10.020 · Cited by 132 · see citing works
Osteopontin Is a Negative Feedback Regulator of Nitric Oxide Synthesis in Murine Macrophages
Guo, H., Cai, C. Q., Schroeder, R. A., & Kuo, P. C. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.2.1079 · Cited by 128 · see citing works
Heguy, A., O’Connor, T. P., Luettich, K., Worgall, S., Cieciuch, A., Harvey, B., Hackett, N. R., & Crystal, R. G. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0008-2 · Cited by 103 · see citing works
Upregulation of Osteopontin by Osteocytes Deprived of Mechanical Loading or Oxygen
Gross, T. S., King, K. A., Rabaia, N. A., Pathare, P. P., & Srinivasan, S. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.041004 · Cited by 82 · see citing works
Osteopontin and Mucosal Protection
Sodek, J., Silva, A. P. B. D., & Zohar, R. (2006) · Journal of Dental Research · doi:10.1177/154405910608500503 · Cited by 81 · see citing works
The Immune System in Space, Including Earth-Based Benefits of Space- Based Research
Sonnenfeld, G. (2005) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201054553699 · Cited by 71 · see citing works
da Silva, A. P. B., Pollett, A. F., Rittling, S. R., Denhardt, D. T., Sodek, J., & Zohar, R. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20701 · Cited by 71 · see citing works
Self-citationOsteopontin: a novel inflammatory mediator of cardiovascular disease
Singh, M. (2006) · Frontiers in bioscience · doi:10.2741/2059 · Cited by 55 · see citing works
Arafat, H. A., Katakam, A. K., Chipitsyna, G. I., Gong, Q., Vancha, A. R., Gabbeta, J., & Dafoe, D. C. (2006) · Endocrinology · doi:10.1210/en.2006-0970 · Cited by 50 · see citing works
Avilés, H., Belay, T., Vance, M., & Sonnenfeld, G. (2005) · NeuroImmunoModulation · doi:10.1159/000084850 · Cited by 42 · see citing works
Ishijima, M., Ezura, Y., Tsuji, K., Rittling, S. R., Kurosawa, H., Denhardt, D. T., Emi, M., Nifuji, A., & Noda, M. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.06.003 · Cited by 38 · see citing works
Self-citationLymphocyte reduction induced by hindlimb unloading: distinct mechanisms in the spleen and thymus
Li Xin, W. E. I., Zhou, J., Roberts, A. I., & Shi, Y. (2003) · Cell Research · doi:10.1038/sj.cr.7290189 · Cited by 37 · see citing works
Self-citationOsteopontin expression and function within the dorsal root ganglion
Marsh, B., Kerr, N. C. H., Isles, N., Denhardt, D. T., & Wynick, D. (2007) · Neuroreport · doi:10.1097/wnr.0b013e328010d4fa · Cited by 24 · see citing works
Self-citationLinkages of nuclear architecture to biological and pathological control of gene expression
Stein, G. S., van Wijnen, A. J., Stein, J. L., Lian, J. B., Pockwinse, S. M., & McNeil, S. M. (1998) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(1998)72:30/31+ · Cited by 6 · see citing works
Self-citationMitogen-Induced Interferon Production by Normal and Steroid-Resistant Mouse Thymocytes
Marcucci, F., Kirchner, H., & Resch, K. (1980) · Journal of Interferon Research · doi:10.1089/jir.1980.1.87 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Osteopontin: role in immune regulation and stress responses
Wang, K. X., & Denhardt, D. T. (2008) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2008.08.001 · Cited by 669 · see citing works
Self-citationHindlimb unloading: rodent analog for microgravity
Globus, R. K., & Morey, E. R. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00997.2015 · Cited by 273 · see citing works
Kazanecki, C. C., Uzwiak, D. J., & Denhardt, D. T. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21558 · Cited by 271 · see citing works
Self-citationChen, Q., Shou, P., Zhang, L., Xu, C., Zheng, C., Han, Y., Li, W., Huang, Y., Zhang, X., Shao, C., et al. (2013) · Stem Cells · doi:10.1002/stem.1567 · Cited by 245 · see citing works
Self-citationEffects of spaceflight on innate immune function and antioxidant gene expression
Baqai, F. P., Gridley, D. S., Slater, J. M., Luo‐Owen, X., Stodieck, L., Ferguson, V. L., Chapes, S. K., & Pecaut, M. J. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91361.2008 · Cited by 174 · see citing works
Tomsia, M., Cieśla, J., Śmieszek, J., Florek, S., Macionga, A. A., Michalczyk, K., & Stygar, D. M. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1284644 · Cited by 112 · see citing works
Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse
Kondo, H., Yumoto, K., Alwood, J. S., Mojarrab, R., Wang, A. Y., Almeida, E. A. C., Searby, N. D., Limoli, C. L., & Globus, R. K. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00294.2009 · Cited by 108 · see citing works
Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro
Prasad, B., Grimm, D. G., Strauch, S. M., Erzinger, G. S., Corydon, T. J., Lebert, M., Magnusson, N. E., Infanger, M., Richter, P. R., & Krüger, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249373 · Cited by 107 · see citing works
PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome
Spinazzi, M., Radaelli, E., Horré, K., Arranz, A. M., Gounko, N. V., Agostinis, P., Maia, T. M., Impens, F., Morais, V. A., López‐Lluch, G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811938116 · Cited by 93 · see citing works
Muscle unloading: A comparison between spaceflight and ground‐based models
Qaisar, R., Karim, A., & Elmoselhi, A. B. (2019) · Acta Physiologica · doi:10.1111/apha.13431 · Cited by 86 · see citing works
Lescale, C., Schenten, V., Djeghloul, D., Bennabi, M., Gaignier, F., Vandamme, K., Strazielle, C., Kuzniak, I., Petite, H., Dosquet, C., et al. (2014) · The FASEB Journal · doi:10.1096/fj.14-259770 · Cited by 73 · see citing works
Gaignier, F., Schenten, V., Bittencourt, M. D. C., Gauquelin‐Koch, G., Frippiat, J., & Legrand-Frossi, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092664 · Cited by 71 · see citing works
Infection-Associated Thymic Atrophy
Luo, M., Xu, L., Qian, Z.-Y., & Sun, X. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.652538 · Cited by 67 · see citing works
Jiang, W., Yu, L., Li, Z., Sun, J., Li, J.-W., Wei, W., Li, L., Zhang, C., Huang, C., Yang, S., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.05.031 · Cited by 66 · see citing works
Changes in Mouse Thymus and Spleen after Return from the STS-135 Mission in Space
Gridley, D. S., Mao, X. W., Stodieck, L., Ferguson, V. L., Bateman, T. A., Moldovan, M., Cunningham, C. E., Jones, T., Slater, J. M., & Pecaut, M. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075097 · Cited by 64 · see citing works
Spleen contributes to restraint stress induced changes in blood leukocytes distribution
Jiang, W., Li, Y., Sun, J., Li, L., Li, J.-W., Zhang, C., Huang, C., Yang, J. J., Kong, G., & Li, Z. (2017) · Scientific Reports · doi:10.1038/s41598-017-06956-9 · Cited by 62 · see citing works
Role of osteopontin in heart failure associated with aging
Singh, M., Foster, C. R., Dalal, S., & Singh, K. (2010) · Heart Failure Reviews · doi:10.1007/s10741-010-9158-6 · Cited by 61 · see citing works
Zhou, Y., Ni, H., Li, M., Sanzari, J. K., Diffenderfer, E. S., Lin, L., Kennedy, A. R., & Weissman, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044329 · Cited by 60 · see citing works
Influence of Social Isolation During Prolonged Simulated Weightlessness by Hindlimb Unloading
Tahimic, C. G. T., Paul, A. M., Schreurs, A., Torres, S. M., Rubinstein, L., Steczina, S., Lowe, M. G., Bhattacharya, S., Alwood, J. S., Ronca, A. E., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01147 · Cited by 58 · see citing works
Dalal, S., Zha, Q., Daniels, C. R., Steagall, R. J., Joyner, W. L., Gadeau, A., Singh, M., & Singh, K. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00954.2013 · Cited by 57 · see citing works
Microgravity Stress: Bone and Connective Tissue
Bloomfield, S. A., Martinez, D. A., Boudreaux, R. D., & Mantri, A. V. (2016) · Comprehensive physiology · doi:10.1002/cphy.c130027 · Cited by 54 · see citing works
Willey, J. S., Britten, R. A., Blaber, E. A., Tahimic, C. G. T., Chancellor, J., Mortreux, M., Sanford, L. D., Kubik, A. J., Delp, M. D., & Mao, X. W. (2021) · Journal of Environmental Science and Health Part C · doi:10.1080/26896583.2021.1885283 · Cited by 53 · see citing works
Osteopontin: At the cross-roads of myocyte survival and myocardial function
Singh, M., Dalal, S., & Singh, K. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.09.014 · Cited by 49 · see citing works
Gruver, A. L., Ventevogel, M. S., & Sempowski, G. D. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0179 · Cited by 47 · see citing works
Li, Y., Jiang, W., Li, Z., Zhang, C., Huang, C. Y., Yang, J. J., Kong, G., & Li, Z. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.11.148 · Cited by 46 · see citing works
Hindlimb suspension and spe-like radiation impairs clearance of bacterial infections
Li, M., Holmes, V., Zhou, Y., Ni, H., Sanzari, J. K., Kennedy, A. R., & Weissman, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085665 · Cited by 43 · see citing works
Lee, W., Milewski, T., Dwortz, M., Young, R. L., Gaudet, A. D., Fonken, L., Champagne, F., & Curley, J. (2022) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2022.04.015 · Cited by 37 · see citing works
Horie, K., Kato, T., Kudo, T., Sasanuma, H., Miyauchi, M., Akiyama, N., Miyao, T., Seki, T., Ishikawa, T., Takakura, Y., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-56432-9 · Cited by 41 · see citing works
Yang, J., Li, J., Cui, X., Li, W., Xue, Y., Shang, P., & Zhang, H. (2019) · Bone · doi:10.1016/j.bone.2019.115108 · Cited by 39 · see citing works
Guo, Q., Chen, N., Patel, K., Wan, M., Zheng, J., & Cao, X. (2023) · Advanced Science · doi:10.1002/advs.202305042 · Cited by 34 · see citing works
Cui, Q., Yang, H., Gu, Y., Zong, C., Chen, X., Lin, Y., Sun, H., Shen, Y., & Zhu, J. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-7400 · Cited by 30 · see citing works
Hind-limb unloading in rodents: Current evidence and perspectives
Hawliczek, A., Brix, B., Mutawa, S. A., Suwaidi, H. S. A., du Plessis, S. S., Gao, Y., Qaisar, R., Siddiqui, R., Elmoselhi, A. B., & Goswami, N. (2022) · Acta Astronautica · doi:10.1016/j.actaastro.2022.03.008 · Cited by 30 · see citing works
Baliga, S. S., Schunke, K. J., Hadzimichalis, N. M., Golfetti, R., & Merrill, G. F. (2010) · Brain Research · doi:10.1016/j.brainres.2010.01.013 · Cited by 28 · see citing works
Toll-Like Receptor 9 Is Required for Chronic Stress-Induced Immune Suppression
Li, H., Zhao, J., Chen, M. J., Tan, Y., Yang, X., Caudle, Y., & Yin, D. (2013) · NeuroImmunoModulation · doi:10.1159/000354610 · Cited by 25 · see citing works
Horie, K., Sasanuma, H., Kudo, T., Fujita, S.-I., Miyauchi, M., Miyao, T., Seki, T., Akiyama, N., Takakura, Y., Shimbo, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-44067-9 · Cited by 25 · see citing works
Wang, K. X., Shi, Y., Ron, Y., Kazanecki, C. C., & Denhardt, D. T. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803023 · Cited by 22 · see citing works
Self-citationWine, E., Shen‐Tu, G., Gareau, M. G., Goldberg, H. A., Licht, C. P. B., Ngan, B., Sørensen, E. S., Greenaway, J. B., Sodek, J., Zohar, R., et al. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091068 · Cited by 20 · see citing works
Ni, H., Balint, K., Zhou, Y., Gridley, D. S., Maks, C., Kennedy, A. R., & Weissman, D. (2011) · Radiation Research · doi:10.1667/rr2373.1 · Cited by 20 · see citing works
Nakamura, T., Shinriki, S., Jono, H., Ueda, M., Nagata, M., Guo, J., Hayashi, M., Yoshida, R., Ota, T., Ota, K., et al. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.12.004 · Cited by 19 · see citing works
Correction: Changes in Mouse Thymus and Spleen after Return from the STS-135 Mission in Space
Gridley, D. S., Mao, X. W., Stodieck, L., Ferguson, V. L., Bateman, T. A., Moldovan, M., Cunningham, C. E., Jones, T., Slater, J. M., & Pecaut, M. J. (2013) · PLoS ONE · doi:10.1371/annotation/e66bdc4e-2409-4582-b163-7bc182db275e · Cited by 19 · see citing works
Rodent retinal microcirculation and visual electrophysiology following simulated microgravity
Dai, X., Ye, S., Chen, X., Jiang, T. X., Huang, H., Li, W., Yu, H., Bao, J., & Chen, H. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108023 · Cited by 18 · see citing works
Sadhukhan, R., Majumdar, D., Garg, S., Landes, R. D., McHargue, V., Pawar, S. A., Chowdhury, P., Griffin, R. J., Narayanasamy, G., Boerma, M., et al. (2020) · Life Sciences in Space Research · doi:10.1016/j.lssr.2020.09.004 · Cited by 18 · see citing works
Osteopontin is associated with inflammation and mortality in a mouse model of polymicrobial sepsis
Fortis, S., Khadaroo, R. G., Haitsma, J. J., & Zhang, H. A. (2014) · Acta Anaesthesiologica Scandinavica · doi:10.1111/aas.12422 · Cited by 17 · see citing works
Li, M., Holmes, V. M., Ni, H., Sanzari, J. K., Romero-Weaver, A. L., Lin, L., Cárabe, A., Diffenderfer, E. S., Kennedy, A. R., & Weissman, D. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120126 · Cited by 15 · see citing works
van den Brûle, S., Huaux, F., Uwambayinema, F., Ibouraadaten, S., Yakoub, Y., Palmai‐Pallag, M., Trottein, F., Renauld, J., & Lison, D. (2013) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0520oc · Cited by 14 · see citing works
Horie, K., Kudo, T., Riko, Y., Akiyama, N., Sasanuma, H., Kobayashi, T., Shimbo, M., Jeon, H., Miyao, T., Miyauchi, M., et al. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.060 · Cited by 14 · see citing works
A mouse model of disuse osteoporosis based on a movable noninvasive 3D-printed unloading device
Li, J., Geng, J., Lin, T., Cai, M., & Sun, Y. (2022) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2021.11.009 · Cited by 13 · see citing works
Mesenchymal stem cells prevent restraint stress-induced lymphocyte depletion via interleukin-4
Cao, G., Yang, Q., Zhang, S., Xu, C., Roberts, A. I., Wang, Y., & Shi, Y. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.01.013 · Cited by 13 · see citing works
Self-citationMatsumoto, Y., Tousen, Y., Nishide, Y., Tadaishi, M., Kato, K., & Ishimi, Y. (2016) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.14-137 · Cited by 10 · see citing works
Social Ecology, Genomics, and African American Health: A Nonlinear Dynamical Perspective
Madhere, S., Harrell, J. P., & Royal, C. D. M. (2009) · Journal of Black Psychology · doi:10.1177/0095798409333587 · Cited by 10 · see citing works
Zhu, H., Zhang, L., Meng, Q., Tuo, S., Fan, F., Li, W., Zhu, S., & Xie, M. (2020) · BioMed Research International · doi:10.1155/2020/2641324 · Cited by 9 · see citing works
Glucocorticoid: A potential role in microgravity-induced bone loss
Yang, J., Yang, Z., Li, W., Xue, Y., Xu, H., Li, J., & Shang, P. (2017) · Acta Astronautica · doi:10.1016/j.actaastro.2017.08.007 · Cited by 9 · see citing works
Acid sphingomyelinase/ceramide regulates carotid intima-media thickness in simulated weightless rats
Cheng, Y., Zhang, H.-J., Su, Y.-T., Meng, X., Xie, X., Chang, Y., & Bao, J. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1969-z · Cited by 9 · see citing works
Booker, C. N., Haga, C. L., Boregowda, S. V., Strivelli, J., & Phinney, D. G. (2021) · npj Microgravity · doi:10.1038/s41526-021-00178-0 · Cited by 9 · see citing works
Horikawa, I., Nagai, H., Taniguchi, M., Chen, G., Shinohara, M., Suzuki, T., Ishii, S., Katayama, Y., Kitaoka, S., & Furuyashiki, T. (2024) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2024.02.010 · Cited by 8 · see citing works
Osa, S., Enoki, Y., Miyajima, T., Akiyama, M., Fujiwara, Y., Taguchi, K., Kim, Y., & Matsumoto, K. (2022) · Shock · doi:10.1097/shk.0000000000002053 · Cited by 8 · see citing works
Mechanisms of lymphoid depletion in bowel obstruction
Lin, Y.-M., Hegde, S., Cong, Y., & Shi, X.-Z. P. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1005088 · Cited by 6 · see citing works
Thymus ad astra, or spaceflight-induced thymic involution
Muramatsu, W., Maryanovich, M., Akiyama, T., & Karagiannis, G. S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1534444 · Cited by 6 · see citing works
Noda, M., & Denhardt, D. T. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00037-9 · Cited by 6 · see citing works
Self-citationPlacenta-Expanded Stromal Cell Therapy in a Rodent Model of Simulated Weightlessness
Rubinstein, L., Paul, A. M., Houseman, C., Abegaz, M., Ruiz, S. T., O’Neil, N., Kunis, G., Ofir, R., Cohen, J., Ronca, A. E., et al. (2021) · Cells · doi:10.3390/cells10040940 · Cited by 6 · see citing works
ADVANCES IN UNDERSTANDING THE SKELETAL BIOLOGY OF SPACEFLIGHT
Globus, R. K., & Morey, E. R. (2011) · Gravitational and Space Research · Cited by 6 · see citing works
Ezura, Y., Nagata, J., Nagao, M., Hemmi, H., Hayata, T., Rittling, S. R., Denhardt, D. T., & Noda, M. (2014) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-014-0568-8 · Cited by 5 · see citing works
Self-citationAghajari, S., Mortazavi, S. M. J., Kalani, M., Nematolahi, S., Habibzadeh, P., & Farjadian, S. (2021) · Europe PMC (PubMed Central) · doi:10.22074/cellj.2021.6856 · Cited by 5 · see citing works
Takahashi, A., Wakihata, S., Ma, L., Adachi, T., Hirose, H., Yoshida, Y., & Ohira, Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123959 · Cited by 5 · see citing works
Physiological effects of environmental enrichment on BALB/c and C57BL/6 strain mice
Gama, L. A., Almeida, M. A. S. O., Souto, P. C. D. S., Bressan, A. F., Giachini, F. R. C., & Américo, M. F. (2025) · Discover Animals · doi:10.1007/s44338-025-00052-3 · Cited by 2 · see citing works
Psychoneuroimmunology and Genetics
Vempati, R. P., & Reddy, H. M. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82557 · Cited by 1 · see citing works
Globus, R. K. (2007) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-008-9013-7
Coyle, L. (2011) · Rutgers University Community Repository (Rutgers University) · doi:10.7282/t36t0m9q
The role of the extracellular matrix in the differentiation of mesenchymal stromal cells
Shou, P., Chen, Q., & Shi, Y. (2016) · Wiley eBooks · doi:10.1002/9781118907474.ch15
Self-citationXing, W., Dong, F., Liu, Y., Yuan, J., Chen, C., Li, Y., Han, W., Yao, M., Chen, T., Cheng, T., et al. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04402-6
- Authors
- Wang, K. X., Shi, Y., & Denhardt, D. T.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- University of Medicine and Dentistry of New Jersey (US)
- Corresponding author
- Denhardt, David T.
- ORCID
- Shi, Yufang
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-09-11
- Volume
- 104
- Issue
- 37
- Pages
- 14777-14782
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1976226
- OpenAlex
- W2089332722
- Cited by
- 73
- References
- 40
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 1 · 2014: 9 · 2013: 5 · 2012: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- osteopontin, hindlimb unloading, microgravity, lymphoid organ atrophy, splenic atrophy, thymic atrophy, corticosterone, T cells, B cells, double-positive thymocytes, weight loss, lymphocyte homeostasis
- MeSH terms
- Adrenal Cortex Hormones, Animals, Anti-Inflammatory Agents, Atrophy, Cell Count, Corticosterone, Dexamethasone, Lymphatic System, Spleen, Thymus Gland, Weight Loss, T-Lymphocyte Subsets, Cytokines, Apoptosis, Mice, Knockout, Fluorescent Antibody Technique, Direct, Hindlimb Suspension, Mice, Osteopontin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
