The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE
Open accessAbstract
High-mobility group box 1 (HMGB1), a nonhistone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine through its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this report, we present evidence for a function of HMGB1 in this event. HMGB1 is released from macrophages in response to RANKL stimulation and is required for RANKL-induced osteoclastogenesis in vitro and in vivo. In addition, HMGB1, like other osteoclastogenic cytokines (e.g., TNFα), enhances RANKL-induced osteoclastogenesis in vivo and in vitro at subthreshold concentrations of RANKL, which alone would be insufficient. The role of HMGB1 in osteoclastogenesis is mediated, in large part, by its interaction with RAGE, an immunoglobin domain containing family receptor that plays an important role in osteoclast terminal differentiation and activation. HMGB1-RAGE signaling seems to be important in regulating actin cytoskeleton reorganization, thereby participating in RANKL-induced and integrin-dependent osteoclastogenesis. Taken together, these observations show a novel function of HMGB1 in osteoclastogenesis and provide a new link between inflammatory mechanisms and bone resorption.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“High mobility group box protein 1 (HMGB1) [198–200] and M-CSF [201] have also been suggested to be produced by osteocytes that stimulate osteoclast recruitment during bone remodeling [72, 73].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [200]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
Lotze, M. T., & Tracey, K. J. (2005) · Nature reviews. Immunology · doi:10.1038/nri1594 · Cited by 2,490
Park, J. S., Svetkauskaite, D., He, Q., Kim, J., Strassheim, D., Ishizaka, A., & Abraham, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306793200 · Cited by 1,582
Lam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11176 · Cited by 1,440 · cited 1×
“text, because release of HMGB1 is elicited by lipopolysaccharide and multiple inflammatory mediators (IL-1, TNF , interferon- and - ), we propose that the HMGB1–RAGE interaction could represent a final common pathway in inflammation-associated bone resorption.((9,35,39))”
BackgroundThe multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses
Schmidt, A. M., Yan, S. D., Yan, S. F., & Stern, D. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14002 · Cited by 1,256
Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A., & Bianchi, M. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg516 · Cited by 1,252
Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis
Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., et al. (2004) · Nature Medicine · doi:10.1038/nm1124 · Cited by 1,170
Cited by
Sorted by citations
Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044
HMGB1 is a therapeutic target for sterile inflammation and infection
Andersson, U., & Tracey, K. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101323 · Cited by 1,437
“Osteoclasts Migration; enhanced osteoclastogenesis and TNF synthesis via HMGB1 interaction with the TNF promoter (80, 140)”
BackgroundCellular signalling of the receptor for advanced glycation end products (RAGE)
Xie, J., Méndez, J. D., Méndez-Valenzuela, V., & Aguilar-Hernández, M. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.013 · Cited by 525
Self-citationHyperglycemia and Glycation in Diabetic Complications
Nègre‐Salvayre, A., Salvayre, R., Augè, N., Pamplona, R., & Portero‐Otín, M. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2484 · Cited by 426
“Various signaling pathways are involved, including JNK, p38, ERK and NF-kB, PKC= pleckstrin (337, 342), as well as interactions with the Toll-like– receptor pathway, as assessed by the inhibitory effect of antibodies directed against TLR4, RAGE, and CD36 (136).”
InfluentialCalcium Phosphate Crystals Induce Cell Death in Human Vascular Smooth Muscle Cells
Ewence, A. E., Bootman, M. D., Roderick, H. L., Skepper, J. N., McCarthy, G., Epple, M., Neumann, M., Shanahan, C. M., & Proudfoot, D. (2008) · Circulation Research · doi:10.1161/circresaha.108.181305 · Cited by 325
Asadipooya, K., & Uy, E. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00160 · Cited by 210
“The pathophysiology of bone impairment includes compromised bone metabolism (due to oxidant injury, lower IGF-1, higher sclerostin, and lower circulating osteoprogenitor cells), impairment of cell function, Abbreviations: ADAM10, a disintegrin and metalloproteinase domain-containing protein 10; AGE, advanced glycation…”
InfluentialEffects of Collagen Crosslinking on Bone Material Properties in Health and Disease
Saito, M., & Marumo, K. (2015) · Calcified Tissue International · doi:10.1007/s00223-015-9985-5 · Cited by 200
de Araújo, A. A., Pereira, A. D. S. B. F., de Medeiros, C. A. C. X., Brito, G. A. D. C., Leitão, R. F. D. C., Araújo, L. D. S., Guedes, P. M. D. M., Hiyari, S., Pirih, F. Q. M., & Júnior, R. F. D. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183506 · Cited by 178
Terkawi, M. A., Matsumae, G., Shimizu, T., Takahashi, D., Kadoya, K., & Iwasaki, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031786 · Cited by 174
Osteocyte apoptosis: the roles and key molecular mechanisms in resorption-related bone diseases
Ru, J., & Wang, Y.-F. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03059-8 · Cited by 159
Diabetes, Collagen, and Bone Quality
Saito, M., Kida, Y., Kato, S., & Marumo, K. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0202-7 · Cited by 152
Davis, H. M., Pacheco‐Costa, R., Atkinson, E. G., Brun, L. R., Gortázar, A. R., Harris, J., Hiasa, M., Bolarinwa, S. A., Yoneda, T., Ivan, M., et al. (2017) · Aging Cell · doi:10.1111/acel.12586 · Cited by 142
“Further, the increased osteoclastogenic potential of Cx43-deficient osteocytes is a result of elevated release of the cytokines RANKL and HMGB1 during apoptosis, and the subsequent activation of RAGE on osteoclast progenitors.”
BackgroundInfluentialOsteogenic Potential of Biosilica on Human Osteoblast-Like (SaOS-2) Cells
Wiens, M., Wang, X., Schloßmacher, U., Lieberwirth, I., Glaßer, G., Ushijima, H., Schröder, H. C., & Müller, W. E. G. (2010) · Calcified Tissue International · doi:10.1007/s00223-010-9408-6 · Cited by 128
“For the experiments, cells were seeded onto Ca–Pcoated coverslips (BioCoat Osteologic coverslips) that had been designed to cultivate osteoblast and osteoclast cells in vitro [32].”
MethodThe role of HMGB1 in the pathogenesis of rheumatic disease
Andersson, U., & Harris, H. E. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2009.11.003 · Cited by 126
Schierbeck, H., Lundbäck, P., Palmblad, K., Klevenvall, L., Erlandsson-Harris, H., Andersson, U., & Ottosson, L. (2011) · Molecular Medicine · doi:10.2119/molmed.2010.00264 · Cited by 122
Morroniside attenuates high glucose–induced BMSC dysfunction by regulating the Glo1/AGE/RAGE axis
Sun, Y., Zhu, Y., Liu, X., Chai, Y., & Xu, J. (2020) · Cell Proliferation · doi:10.1111/cpr.12866 · Cited by 107
APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age-dependent manner
Cui, S., Xiong, F., Hong, Y., Jung, J.-U., Li, X.-S., Liu, J.-Z., Yan, R., Mei, L., Feng, X., & Xiong, W.-C. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.299 · Cited by 101
“We thus have further investigated functions of RAGE ligands in OC differentiation and activation and have demonstrated that HMGB1, a proinflammatory cytokine released from activated macrophages, promotes RANKL-induced OC differentiation in a RAGE-dependent manner.((28)) The RAGE ligands AGE and S100 are also found to…”
BackgroundMethodInfluentialSelf-citationRelevance of Nrf2 and heme oxygenase-1 in articular diseases
Alcaraz, M. J., & Ferrándiz, M. L. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.12.007 · Cited by 98
Yamamoto, M., Yamaguchi, T., Yamauchi, M., & Sugimoto, T. (2009) · Diabetes Care · doi:10.2337/dc09-0901 · Cited by 96
Apoptotic Osteocytes and the Control of Targeted Bone Resorption
Plotkin, L. I. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0194-3 · Cited by 93
Prantner, D., Nallar, S., & Vogel, S. N. (2020) · The FASEB Journal · doi:10.1096/fj.202002136r · Cited by 92
Wei, L., Chen, W., Huang, L., Wang, H., Su, Y., Liang, J., Lian, H., Xu, J., Zhao, J., & Liu, Q. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106400 · Cited by 92
Cheung, W. Y., Fritton, J. C., Morgan, S. A., Seref-Ferlengez, Z., Basta-Pljakic, J., Thi, M. M., Suadicani, S. O., Spray, D. C., Majeska, R. J., & Schaffler, M. B. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2740 · Cited by 89
“Bidwell and colleagues showed that apoptotic MLO-Y4 cells release HMGB1, which stimulated TNFa and RANKL synthesis in bone marrow stromal cells.((12,14,62)) In vivo confirmation of this mechanism is lacking.”
BackgroundSaito, M., & Marumo, K. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00072 · Cited by 88
“The extracellular HMGB1, through RAGE, in large, regulates osteoclastic actin cytoskeleton remodeling, differentiation, and function (Zhou et al., 2008).”
BackgroundXia, W.-F., Jung, J.-U., Cui, S., Xiong, S., Xiong, L., Shi, X., Mei, L., & Xiong, W. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1954 · Cited by 91
“Bone histomorphometric analyses were carried out as described.((21,22,28)) In brief, mouse tibias and femurs were fixed overnight in 10% buffered formalin, decalcified in 14% EDTA, embedded in paraffin, sectioned, and subjected to hematoxylin and eosin (H&E) and Goldner’s trichrome stain analyses, which were counterst…”
MethodSelf-citationCavati, G., Pirrotta, F., Merlotti, D., Ceccarelli, E., Calabrese, M., Gennari, L., & Mingiano, C. (2023) · Antioxidants · doi:10.3390/antiox12040928 · Cited by 84
“Studies on the silenced RAGE gene have demonstrated an attenuation of RANKL-mediated osteoclastic differentiation [33], with reduced bone resorption, reduced osteoclast number, and increased bone mass [34].”
BackgroundEndo‐Munoz, L., Cumming, A., Sommerville, S. M. M., Dickinson, I. C., & Saunders, N. A. (2010) · British Journal of Cancer · doi:10.1038/sj.bjc.6605723 · Cited by 75
“…(Pereira et al, 1990; Garcia et al, 1996; Lowell et al, 1996; Chertov et al, 1997; Chellaiah et al, 2000; Duong et al, 2000; Battaglino et al, 2002; Lundberg et al, 2007; Shahbazi et al, 2007; Kawano et al, 2008; Zhou et al, 2008; Soehnlein and Lindbom, 2009) was observed in the OS biopsies.”
Abdominal drains: a brief historical review.
Memon, M. A., Memon, M. A., & Donohue, J. H. (2001) · PubMed · Cited by 72
Pereira, A. D. S. B. F., Brito, G. A. D. C., Lima, M. L. D. S., da Silva-Júnior, A. A., Silva, E. D. S., de Rezende, A. A., Bortolin, R. H., Galvan, M., Pirih, F. Q. M., Júnior, R. F. D. A., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113488 · Cited by 73
“HMGB1 acts by stimulating the differentiation of osteoclast precursors in the presence of RANKL, and has similar proinflammatory properties to cytokines once it enters the extracellular space [36].”
BackgroundCirculating HMGB1 and RAGE as Clinical Biomarkers in Malignant and Autoimmune Diseases
Pilzweger, C., & Holdenrieder, S. (2015) · Diagnostics · doi:10.3390/diagnostics5020219 · Cited by 67
“and thus an additional destructive effect on joint tissue in RA [157,158].”
BackgroundThe role of high mobility group box chromosomal protein 1 in rheumatoid arthritis
Chen, Y., Sun, W., Gao, R., Su, Y., Umehara, H., Dong, L., & Gong, F. (2013) · Rheumatology · doi:10.1093/rheumatology/ket134 · Cited by 66
Bone and the Innate Immune System
Charles, J. F., & Nakamura, M. C. (2014) · Current Osteoporosis Reports · doi:10.1007/s11914-014-0195-2 · Cited by 58
Pan, J.-X., Tang, F., Xiong, F., Xiong, L., Zeng, P., Wang, B., Zhao, K., Guo, H., Shun, C., Xia, W.-F., et al. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-1123-7 · Cited by 59
Self-citationSakai, E., Shimada‐Sugawara, M., Nishishita, K., Fukuma, Y., Naito, M., Okamoto, K., Nakayama, K., & Tsukuba, T. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23372 · Cited by 60
“Zhou et al. (2008) demonstrated that RANKL induces HMGB1 release during an early stage of differentiation from BMMs into osteoclasts.”
BackgroundInfluentialÖstberg, T., Kawane, K., Nagata, S., Yang, H., Chavan, S. S., Klevenvall, L., Bianchi, M. E., Harris, H. E., Andersson, U., & Palmblad, K. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27590 · Cited by 58
Kozakowska, M., Szade, K., Dulak, J., & Józkowicz, A. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5341 · Cited by 56
“Recently, the high mobility group box 1 (HMGB1) nuclear transcription factor, which can be released by damaged cells, was shown to upregulate maturation of osteoclasts by binding to advanced glycation endproduct receptors (254).”
BackgroundRAGE Signaling in Skeletal Biology
Plotkin, L. I., Essex, A. L., & Davis, H. M. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00499-w · Cited by 54
Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review
Martinis, M. D., Ginaldi, L., Sirufo, M. M., Pioggia, G., Calapai, G., Gangemi, S., & Mannucci, C. (2020) · Medicina · doi:10.3390/medicina56030138 · Cited by 54
“Evidence supporting the role of extracellular HMGB1, as an autocrine ligand of RAGE, in RANKL-induced osteoclastogenesis in vitro and in vivo have been proposed [63].”
BackgroundWang, X., Schröder, H. C., Feng, Q., Draenert, F. G., & Müller, W. E. G. (2013) · Marine Drugs · doi:10.3390/md11030718 · Cited by 49
“osteoprotegerin (OPG), a cytokine that is expressed in osteoblasts with a significant role in the maturation of osteoclasts as well as in the control of bone mineral density [41], and the receptor activator of the NF-κB ligand (RANKL), a mediator that binds to RANK which is a receptor that mediates maturation of osteo…”
BackgroundPieters, B. C. H., Cappariello, A., van den Bosch, M. H. J., van Lent, P. L. E. M., Teti, A. M., & van de Loo, F. A. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01901 · Cited by 50
“HMGB1-RAGE signaling was shown to be important in regulating actin cytoskeleton reorganization, thereby contributing to RANKL-induced and integrin-dependent osteoclastogenesis (81).”
BackgroundHigh Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies
Datta, S., Rahman, M. A., Koka, S., & Boini, K. M. (2024) · Cells · doi:10.3390/cells13231946 · Cited by 48
Dual effect of inorganic polymeric phosphate/polyphosphate on osteoblasts and osteoclasts in vitro
Wang, X., Schröder, H. C., Diehl‐Seifert, B., Kropf, K., Schloßmacher, U., Wiens, M., & Müller, W. E. G. (2012) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.1465 · Cited by 48
“RANKL results in the accelerated maturation of osteoclast precursor cells (Zhou et al., 2008), a signalling which is”
BackgroundInfluentialXia, W.-F., Tang, F., Xiong, L., Xiong, S., Jung, J.-U., Lee, D.-H., Li, X.-S., Feng, X., Mei, L., & Xiong, W. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201207154 · Cited by 50
“Bone histomorphometric analyses were performed as previously described (Zhou et al., 2006, 2008; Cui et al., 2011).”
MethodSelf-citationRAGE and its ligands in bone metabolism
Xiong, W.-C. (2010) · Frontiers in Bioscience-Scholar · doi:10.2741/s185 · Cited by 45
Self-citationRoles of Toll-like Receptor Signaling in Inflammatory Bone Resorption
Tominari, T., Matsumoto, C., Tanaka, Y., Shimizu, K., Takatoya, M., Sugasaki, M., Karouji, K., Kasuga, U., Miyaura, C., Miyata, S., et al. (2024) · Biology · doi:10.3390/biology13090692 · Cited by 42
“Several DAMPs derived from dead cells have been reported to function as endogenous TLR4 ligands, including high-mobility group box 1 (HMGB1) and S100 proteins, which induce osteoclastic bone resorption [42–44].”
BackgroundMovilă, A., Ishii, T., Albassam, A., Wisitrasameewong, W., Howait, M., Yamaguchi, T., Ruiz‐Torruella, M., Bahammam, L. A., Nishimura, K., Dyke, T. E. V., et al. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2854 · Cited by 43
“Although it is true that the positive effects of HMGB1 on bone resorption are well established,((58)) the roles played by the HMGB1/MIF complex in the migration of OCPs and osteoclastogenesis are unknown.”
BackgroundProgress and Applications of Polyphosphate in Bone and Cartilage Regeneration
Wang, Y., Li, M., Li, P., Teng, H., Fan, D., Du, W., & Guo, Z. (2019) · BioMed Research International · doi:10.1155/2019/5141204 · Cited by 46
“The interaction between RANKL produced by osteoblasts and its receptor RANK can induce (pre)osteoclasts differentiation [22, 64].”
BackgroundHMGB1 Localization during Experimental Periodontitis
Nogueira, A. V. B., de Souza, J. A. C., de Molon, R. S., Pereira, E. D. S. M., de Aquino, S. G., Giannobile, W. V., & Cirelli, J. A. (2014) · Mediators of Inflammation · doi:10.1155/2014/816320 · Cited by 40
“In vivo studies have shown similar results indicating that, in the presence of extracellular HMGB1, RANKL is able to induce more evident osteoclastogenesis [7].”
BackgroundResultActivation of cannabinoid receptors promote periodontal cell adhesion and migration
Liu, C., Qi, X., Alhabeil, J. A., Lu, H., & Zhou, Z. (2019) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.13190 · Cited by 40
Self-citationPYK2 interacts with MyD88 and regulates MyD88-mediated NF-κB activation in macrophages
Xi, C.-X., Xiong, F., Zhou, Z., Mei, L., & Xiong, W. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0309125 · Cited by 38
“in 5% CO2 as previously described [17].”
Self-citationEarly stage blockade of the alarmin HMGB1 reduces cartilage destruction in experimental OA
Aulin, C., Lassacher, T. M., Palmblad, K., & Harris, H. E. (2020) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2020.01.003 · Cited by 38
The Role of Oxidative Stress in Aseptic Loosening of Total Hip Arthroplasties
Steinbeck, M. J., Delaney, L. J., Parvizi, J., & Freeman, T. A. (2013) · The Journal of Arthroplasty · doi:10.1016/j.arth.2013.09.001 · Cited by 37
“Finally, HMGB1 was evaluated, as it is an oxidative stress responsive protein required for RANKL-induced osteoclastogenesis [31].”
Martinotti, S., Patrone, M., Manfredi, M., Gosetti, F., Pedrazzi, M., Marengo, E., & Ranzato, E. (2016) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25549 · Cited by 37
Irradiation‐induced osteocyte damage promotes HMGB1‐mediated osteoclastogenesis in vitro
He, F., Bai, J., Wang, J., Zhai, J., Tong, L., & Zhu, G. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28351 · Cited by 37
“Moreover, extracellular HMGB1 has proved to support the generation of osteoclasts (Zhou et al., 2008).”
BackgroundChen, Y., Wang, Y., Tang, R., Yang, J., Dou, C., Dong, Y., Sun, D., Zhang, C., Zhang, L., Tang, Y., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2612-z · Cited by 38
HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization
Chen, Q., Bei, J.-J., Liu, C., Feng, S.-B., Zhao, W.-B., Zhou, Z., Yu, Z.-P., Du, X.-J., & Hu, H.-Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156686 · Cited by 38
“HMGB1, a nuclear protein released from stressed cells, has been indicated as a bone-active cytokine [17] and involved in ossification, arthritis and ectopic mineralization pathogenesis [18, 31].”
BackgroundSelf-citationFumimoto, R., Sakai, E., Yamaguchi, Y., Sakamoto, H., Fukuma, Y., Nishishita, K., Okamoto, K., & Tsukuba, T. (2012) · Journal of Pharmacological Sciences · doi:10.1254/jphs.11212fp · Cited by 36
Okui, T., Hiasa, M., Ryumon, S., Ono, K., Kunisada, Y., Ibaragi, S., Sasaki, A., Roodman, G. D., White, F. A., & Yoneda, T. (2020) · Journal of bone oncology · doi:10.1016/j.jbo.2020.100330 · Cited by 34
“A previous study described that HMGB1 increases RANKLinduced osteoclastogenesis via activating RAGE, but not TRL4, signaling [34].”
BackgroundResultPullerits, R., Forsblad‐d’Elia, H., Tarkowski, A., & Carlsten, H. (2009) · Rheumatology · doi:10.1093/rheumatology/kep079 · Cited by 33
Davis, H. M., Valdez, S., Gomez, L., Malicky, P., White, F. A., Subler, M. A., Windle, J. J., Bidwell, J. P., Bruzzaniti, A., & Plotkin, L. I. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28932 · Cited by 31
“In osteoclasts, HMGB1‐RAGE signaling regulates RANKL‐induced osteoclast differentiation and activity.(25) Further, epidermal growth factor‐mediated HMGB1 release induces RANK expression via CD68 in patients with autoimmune disease, suggesting that extracellular HMGB1 promotes osteoclast differentiation in human diseas…”
BackgroundDeng, Z., Ren, Y., Park, M. S., & Kim, H. K. W. (2021) · Bone · doi:10.1016/j.bone.2021.116215 · Cited by 33
The Load-Bearing Mechanosome Revisited
Bidwell, J. P., & Pavalko, F. M. (2010) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-010-9075-1 · Cited by 32
“RANKL stimulates HMGB1 release from macrophages [86] and PTH attenuates the release of HMGB1 from osteoblasts by repressing apoptosis [87].”
BackgroundLiou, S., Hsu, J., Lin, I., Ho, M., Hsu, P.-C., Chen, L., Chen, I., & Yeh, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069468 · Cited by 29
“It has been demonstrated that release of extracellular HMGB1 can be induced by RANKL during an early stage of differentiation from BMMs into osteoclasts, and HMGB1 is believed as a critical mediator participating in RANKL-induced and integrin-dependent osteoclastogenesis [25].”
BackgroundInfluentialXiong, L., Xia, W.-F., Tang, F.-L., Pan, J., Mei, L., & Xiong, W. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.05.028 · Cited by 29
“Bonehistomorphometric analyseswere carried out as previously described (Cui et al., 2010; Xia et al., 2013a; Xia et al., 2013b; Zhou et al., 2008; Zhou et al., 2006).”
MethodSelf-citationFrom death to birth: how osteocyte death promotes osteoclast formation
Zhao, W., Qian, J., Li, J., Su, T., Deng, X., Fu, Y., Liang, X., & Cui, H. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1551542 · Cited by 28
“HMGB1 can also directly act on OCPs and osteoclasts to induce osteoclast differentiation through RAGE and TLR4 activation (13).”
InfluentialtBHQ Suppresses Osteoclastic Resorption in Xenogeneic‐Treated Dentin Matrix‐Based Scaffolds
Sun, J., Li, J., Li, H., Yang, H., Chen, J., Yang, B., Huo, F., Guo, W., & Tian, W. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700127 · Cited by 27
Yamamoto, M., Sakiyama, K., Kitamura, K., Yamamoto, Y., Takagi, T., Sekiya, S., Watanabe, G., Taniguchi, S., Ogawa, Y., Ishizuka, S., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063006 · Cited by 27
HMGB1‐induced inflammatory response promotes bone healing in murine tooth extraction socket
Aoyagi, H., Yamashiro, K., Yoshihara‐Hirata, C., Ideguchi, H., Yamasaki, M., Kawamura, M., Yamamoto, T., Kochi, S., Wake, H., Nishibori, M., et al. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26710 · Cited by 28
“Recently, Xue et al reported that recombinant HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets accelerates bone fracture healing.(9) In a future study, we will try to use the recombinantHMGB1protein to examinewhether it promotes bone healing in the tooth extraction socket.”
BackgroundPARP1 Hinders Histone H2B Occupancy at the NFATc1 Promoter to Restrain Osteoclast Differentiation
Wang, C., Xiao, J., Nowak, K., Gunasekera, K., Alippe, Y., Speckman, S., Yang, T., Kress, D., Abu‐Amer, Y., Hottiger, M. O., et al. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3927 · Cited by 23
“Other modified proteins included PARP1 itself, PARP14, heterogeneous ribonucleoproteins (hnRNPs), and high-mobility group box 1 (HMGB1), a well-characterized stimulator of OC formation.((73)) Western blot analysis using H2B antibody revealed no changes in the global levels of ADP-ribosylated H2B between macs and pOCs,…”
BackgroundSelf-citationRAGE supports parathyroid hormone-induced gains in femoral trabecular bone
Philip, B. K., Childress, P., Robling, A. G., Heller, A., Nawroth, P. P., Bierhaus, A., & Bidwell, J. P. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00564.2009 · Cited by 26
“Our comprehensive longitudinal analysis of the Rage-KO mouse during anabolic PTH treatment reveals a more complex skeletal phenotype than reported previously (11, 38) and suggests deficits in both the osteogenic and osteoclastic arms of skeletal homeostasis, which is consistent with recent studies showing a role for R…”
BackgroundResultInfluentialrhHMGB1 drives osteoblast migration in a TLR2/TLR4- and NF-κB-dependent manner
Li, M.-J., Li, F., Xu, J., Liu, Y., Hu, T., & Chen, J.-T. (2016) · Bioscience Reports · doi:10.1042/bsr20150239 · Cited by 26
Hou, C., Luan, L., & Ren, C. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.11.083 · Cited by 25
Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling
Lu, L., Rao, L., Jia, H., Chen, J., Lu, X., Yang, G., Li, Q., Lee, K. K., & Yang, L. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13066 · Cited by 24
S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis
Kim, H., Kim, S. I., Kim, S. I., Kim, H. J., Ryu, B. Y., Chung, J., Lee, Z. H., & Kim, H. (2019) · Bone Research · doi:10.1038/s41413-019-0068-5 · Cited by 24
Lin, Y., Zheng, G. H., Liu, H., Wang, P., Yuan, W.-Q., Zhang, Y., Peng, X., Li, G.-J., Wu, Y., & Shen, H. (2023) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2023.05.007 · Cited by 25
“Previous studies have shown that the expression of HMGB1 is upregulated during the osteoclast differentiation of CD14þ PBMCs induced by RANKL in vitro, and the recombination of the actin cytoskeleton of osteoclasts is regulated by the receptor for advanced glycation end products (RAGE) [34].”
BackgroundGuo, J.-P., Pan, J., Xiong, L., Xia, W.-F., Cui, S., & Xiong, W. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139395 · Cited by 24
“ThemicroCT analysis was carried out as described previously [17, 18].”
MethodInfluentialSelf-citationWolf, M. F., Lossdörfer, S., Küpper, K., & Jäger, A. (2013) · European Journal of Orthodontics · doi:10.1093/ejo/cjt037 · Cited by 23
The RAGE signaling in osteoporosis
Zhou, J., Liu, S., Bi, S., Kong, W., Qian, R., Xie, X., Zeng, M., Jiang, X., Liao, Z., Shuai, M., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115044 · Cited by 23
Wolf, M. F., Lossdörfer, S., Craveiro, R. B., Götz, W., & Jäger, A. (2013) · Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie · doi:10.1007/s00056-013-0167-7 · Cited by 22
Roles of High Mobility Group Box 1 in Cardiovascular Calcification
Chen, Q., Wang, Z., Chen, L., & Hu, H. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000477591 · Cited by 22
Sakamoto, Y., Okui, T., Yoneda, T., Ryumon, S., Nakamura, T., Kawai, H., Kunisada, Y., Ibaragi, S., Masui, M., Ono, K., et al. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.07.120 · Cited by 20
“Some reports indicated that HMGB1 directly promotes maturation of osteoclasts independent of RANKL signaling [12].”
BackgroundInfluentialSoluble CD93 lectin-like domain sequesters HMGB1 to ameliorate inflammatory diseases
Huang, S., Kuo, C., Shiao, S.-Y., Shen, C., Lee, F.-T., Chang, B.-I., Hsu, J., Wu, H., Yeh, J., & Lai, C. (2023) · Theranostics · doi:10.7150/thno.84935 · Cited by 20
“Immunofluorescence staining showed that RANKL stimulation substantially accentuated the staining of HMGB1 that was colocalized with F-actin (Figure S5B), a prerequisite cytoplasmic structure for osteoclast bone resorption [34].”
BackgroundResultInfluentialLiu, B., Gan, X., Zhao, Y., Yu, H., Gao, J., & Yu, H. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/1703709 · Cited by 20
“Moreover, studies have shown that in osteoclast precursor cells, RAGE appears to be required for integrin signaling and the cross-talk between HMGB1 and integrin signaling [39].”
BackgroundYamaguchi, Y., Sakai, E., Sakamoto, H., Fumimoto, R., Fukuma, Y., Nishishita, K., Okamoto, K., & Tsukuba, T. (2012) · Journal of Applied Toxicology · doi:10.1002/jat.2827 · Cited by 19
“…HMGB1, which acts as a proinflammatory cytokine, can bind to cell-surface receptors such as the receptor for advanced glycation end products and Toll-like receptors 2 and 4, and modulate differentiation of OCL precursors in the presence of RANKL (Yamoah et al., 2008; Zhou et al., 2008).”
BackgroundResultInfluentialMechanisms of Osteoinduction/Chondroinduction by Demineralized Bone
Glowacki, J., Zhou, S., & Mizuno, S. (2009) · Journal of Craniofacial Surgery · doi:10.1097/scs.0b013e3181928077 · Cited by 18
Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss
Cheng, T., Lai, C., Shieh, S.-J., Jou, Y.-B., Yeh, J., Yang, A.-L., Wang, Y., Wang, C., Chen, C., Shi, G.-Y., et al. (2016) · Scientific Reports · doi:10.1038/srep28340 · Cited by 18
Self-citationTakahashi, T., Katsuta, S., Tamura, Y., Nagase, N., Suzuki, K. W., Nomura, M., Tomatsu, S., Miyamoto, K., & Kobayashi, S. (2013) · Molecular Medicine · doi:10.2119/molmed.2012.00309 · Cited by 18
Deltamethrin inhibits osteoclast differentiation via regulation of heme oxygenase-1 and NFATc1
Sakamoto, H., Sakai, E., Fumimoto, R., Yamaguchi, Y., Fukuma, Y., Nishishita, K., Okamoto, K., & Tsukuba, T. (2012) · Toxicology in Vitro · doi:10.1016/j.tiv.2012.05.005 · Cited by 17
Nishioku, T., Toshiki, K. U. B. O., KAMADA, T., Okamoto, K., Tsukuba, T., Uto, T., & Shoyama, Y. (2020) · Biomedical Research · doi:10.2220/biomedres.41.269 · Cited by 17
“It has been shown that extracellular HMGB1 interacts with RAGE during osteoclastogenesis (Zhou et al. 2008).”
BackgroundInfluentialNishioku, T., Kawamoto, M., Okizono, R., Sakai, E., Okamoto, K., & Tsukuba, T. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.088 · Cited by 16
Wolf, M. F., Lossdörfer, S., Craveiro, R. B., & Jäger, A. (2013) · Innate Immunity · doi:10.1177/1753425913505121 · Cited by 16
“osteoclastic differentiation.(21) Sha et al.”
Kim, H. K. W., Park, M. S., do Monte, F. A., Gokani, V., Aruwajoye, O. O., & Ren, Y. (2021) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.20.00578 · Cited by 15
Li, M., Ong, C. Y., Langouët-Astrié, C. J., Tan, L., Verma, A., Yang, Y., Zhang, X., Shah, D. K., Schmidt, E. P., & Xu, D. (2022) · eLife · doi:10.7554/elife.71403 · Cited by 15
Hui, P., Zhou, S., Cao, C., Zhao, W., Zeng, L., & Rong, X. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1195567 · Cited by 14
“HMGB1 has been demonstrated to play an essential role in autoimmune diseases such as rheumatoid arthritis (RA), as well as in inflammatory events (Zhou et al., 2008).”
BackgroundOyama, M., Ukai, T., Yamashita, Y., & Yoshimura, A. (2020) · Journal of Periodontal Research · doi:10.1111/jre.12813 · Cited by 14
Monir, A., Mukaibo, T., Abdelaal, A., Nodai, T., Munemasa, T., Kondo, Y., Masaki, C., El-Shair, M. A., Matsuo, K., & Hosokawa, R. (2021) · Scientific Reports · doi:10.1038/s41598-021-88195-7 · Cited by 14
Bone matrix quality in a developing high-fat diet mouse model is altered by RAGE deletion
Stephen, S. J., Bailey, S., D'Erminio, D. N., Krishnamoorthy, D., Iatridis, J. C., & Vashishth, D. (2022) · Bone · doi:10.1016/j.bone.2022.116470 · Cited by 14
Chang, L., Lai, C., Kuo, C., Chang, B.-I., Wu, H., & Cheng, T. (2021) · Journal of Periodontology · doi:10.1002/jper.20-0732 · Cited by 17
Turner, M. E., Bartoli‐Leonard, F., & Aïkawa, E. (2022) · Immunological Reviews · doi:10.1111/imr.13134 · Cited by 15
Yang, X. Y., Gandhi, C., Rahman, M. M., Appleford, M. R., Sun, L.-W., & Wang, X. (2015) · Calcified Tissue International · doi:10.1007/s00223-015-0042-1 · Cited by 13
Metadata
- Authors
- Zhou, Z., Han, J.-Y., Xi, C.-X., Xie, J.-X., Feng, X., Wang, C.-Y., Mei, L., & Xiong, W.-C.
- Affiliations
- Augusta University (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Xiong, Wen-Cheng
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-07-01
- Volume
- 23
- Issue
- 7
- Pages
- 1084-1096
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC2679382
- OpenAlex
- W2126202075
- Cited by
- 160
- References
- 43
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 7 · 2014: 6 · 2013: 16 · 2012: 5
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR048120, AR048120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- HMGB1, RANKL, osteoclastogenesis, RAGE, receptor for advanced glycation end products, macrophages, bone resorption, actin cytoskeleton remodeling, integrin signaling, inflammatory bone loss, extracellular HMGB1
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Base Sequence, Cell Division, Fluorescent Antibody Technique, Osteoclasts, Receptors, Immunologic, Blotting, Western, DNA Primers, Mice, Knockout, HMGB1 Protein, Mice, RANK Ligand
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
