Regulation of NFATc1 in Osteoclast Differentiation
Open accessAbstract
Osteoclasts are unique cells that degrade the bone matrix. These large multinucleated cells differentiate from the monocyte/macrophage lineage upon stimulation by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL). Activation of transcription factors such as microphthalmia transcription factor (MITF), c-Fos, NF-κB, and nuclear factor-activated T cells c1 (NFATc1) is required for sufficient osteoclast differentiation. In particular, NFATc1 plays the role of a master transcription regulator of osteoclast differentiation. To date, several mechanisms, including transcription, methylation, ubiquitination, acetylation, and non-coding RNAs, have been shown to regulate expression and activation of NFATc1. In this review, we have summarized the various mechanisms that control NFATc1 regulation during osteoclast differentiation.
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NFATc1 binds to its own promoter, switching on an epigenetically controlled autoregulatory cycle that permits efficient induction of TRAP, cathepsin K, DC-STAMP, and ATP6v0d2.
“NFATc1 binds to its own promoter, switching on an epigenetically controlled autoregulatory cycle that permits efficient induction of the osteoclast-specific genes, tartrate-resistant acid phosphatase (TRAP), cathepsin K, as well as the fusion-specific genes, dendritic cell-specific transmembrane protein (DC-STAMP) and ATPase H+ transporting V0 subunit D2 (ATP6v0d2) [20,25,26] (Figure 3).”
From Osteoclasts and Microgravity (2020) · cites this paper as [20]
The 'Transcriptional regulation of NFATc1 in osteoclasts' section (page not provided) reports recruitment of NFATc1 to its own promoter and an epigenetically supported autoregulatory loop. The Introduction (page not provided) identifies TRAP and cathepsin K as NFATc1-regulated genes, but our copy does not identify DC-STAMP or ATP6v0d2 as targets or establish that the loop permits induction of all four genes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn RANKL-activated HSCs, polyubiquitination of NIK is inhibited and TRAF6 activates a cascade of kinases including ERK, p38, JNK, PI3K, Akt, and IkB kinases.
“In RANKL-activated HSCs, polyubiquitination of NIK is inhibited [18], and TRAF6 activates a cascade of kinases, including extracellular regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), c-jun N-terminal kinase (JNK), phosphatidylinositol-3 kinase (PI3K), and Akt and IkB kinases [20,21].”
From Osteoclasts and Microgravity (2020) · cites this paper as [20]
The Introduction says RANKL recruits TRAF6 and links it to downstream ERK, p38, and JNK signaling in osteoclast precursor cells. The transcriptional-regulation section describes IκB kinases in RANKL signaling, but does not link them specifically to TRAF6; the cited passages do not establish PI3K or Akt activation or identify the cells as HSCs. The NIK-polyubiquitination clause carries a separate citation [18], so it is not assessed against this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe RANKL-activated kinase cascade requires Lys63-linked TRAF-6 auto-ubiquitination and initiates transcription of AP-1, c-Fos, NF-κB, and NFATc1, the master regulator of osteoclast differentiation.
“This cascade requires Lys63-linked TRAF-6 auto-ubiquitination [22] and initiates the transcription of activator protein-1 (AP-1), c-Fos, NF-κB, and nuclear factor of activated T cells cytoplasmic calcineurin-dependent 1 (NFATc1), the master regulator of osteoclast differentiation [20,23,24].”
From Osteoclasts and Microgravity (2020) · cites this paper as [20]
The Introduction says RANKL recruits TRAF6 and activates downstream pathways and transcription factors including NF-κB, c-Fos, and NFATc1. The section on transcriptional regulation identifies c-Fos as an AP-1 member, describes RANKL-induced NFATc1 expression, and calls NFATc1 a master factor. It does not say that the cascade initiates transcription of AP-1 and NF-κB; it describes their activation instead. The Lys63-linked TRAF6 auto-ubiquitination clause has its own citation [22] and is not assessed against this source. (LLM, conf=0.85)
Experimental — accuracy not yet measuredAmong genes harboring an excess of HF SNCs associated with specific facial features, we find RUNX2, EDAR, GLI3, NFATC1, SPOP, DDR2 and NELL1, possibly carrying changes in regulatory regions.
“Among genes harboring an excess of HF SNCs associated with specific facial features, we find RUNX2, EDAR, and GLI3133, NFATC1134, SPOP135, DDR2136 and NELL1137, possibly carrying changes in regulatory regions”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [134]
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The role of NFAT in osteoclast formation
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“This leads to their translocation from the cytosol to the nucleus, where they regulate the target genes.[21,22] There is a high degree of structural similarity among the different members of the NFAT family, which allows for redundancy in some NFAT functions in T cells.”
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“In addition, the Ca2+ chelator BAPTA-AM suppresses osteoclast differentiation mediated by RANKL through the inhibition of nuclear localization of NFATc1.”
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“Several kinases such as glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), p38, and JNK phosphorylate the various serine-rich motifs in NFAT proteins, thereby preventing translocation into the nucleus or promoting nuclear export of NFAT proteins.[59-63] A recent study has reported that the ectopic expression of…”
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Novack, D., Yin, L., Hagen-Stapleton, A., Schreiber, R. D., Goeddel, D., Ross, F. P., & Teitelbaum, S. L. (2003) · Journal of Experimental Medicine · doi:10.1084/jem.20030116 · Cited by 275 · see citing works
MafB negatively regulates RANKL-mediated osteoclast differentiation
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“[32,33] In the alternative pathway, NF-κB-inducing kinase (NIK) and IKKα phosphorylate and process p100 to generate p52 by proteasomes, resulting in the activation of the p52/RelB complex.[32-35] The important role played by NF-κB proteins in osteoclastogenesis has been verified by the severe osteopetrotic phenotype o…”
BackgroundKim, K., Kim, J. H., Lee, J., Jin, H., Lee, S., Fisher, D. E., Kook, H. Y., Kim, K. K., Choi, Y., & Kim, N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505815200 · Cited by 247 · cited 1× · see citing works
“In particular, NFATc1, a master regulator of osteoclast differentiation, regulates a number of osteoclast specific genes such as TRAP, cathepsin K, calcitonin receptor, and osteoclast-associated receptor (OSCAR) through cooperation with MITF and c-Fos.[10-13] The essential role of NFATc1 in osteoclast differentiation…”
BackgroundSelf-citationBridging the NFAT and NF-κB Families
López‐Rodríguez, C., Aramburu, J. F., Jin, L., Rakeman, A. S., Michino, M., & Rao, A. (2001) · Immunity · doi:10.1016/s1074-7613(01)00165-0 · Cited by 239 · see citing works
NFAT signaling in vertebrate development
Graef, I. A., Chen, F., & Crabtree, G. R. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00225-2 · Cited by 215 · cited 1× · see citing works
“Since the discovery of the first NFAT protein, NFATs have been discovered to be involved in immune cell activation, heart valve formation, cardiac hypertrophy, and osteoclast development.[16-19] However, the function and regulation of NFAT proteins is best understood in T cells.”
BackgroundPLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2
Mao, D., Epple, H., Uthgenannt, B., Novack, D. V., & Faccio, R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28775 · Cited by 214 · cited 1× · see citing works
“[58] Well known inhibitors of calcineurin, such as FK506 and cyclosporine A, strongly inhibit RANKL-induced osteoclast differentiation by blocking NFATc1 translocation into the nucleus in vitro and in vivo.”
BackgroundThe Blimp1–Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis
Miyauchi, Y., Ninomiya, K., Miyamoto, H., Sakamoto, A., Iwasaki, R., Hoshi, H., Miyamoto, K., Wu, H., Yoshida, S., Morioka, H., et al. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091957 · Cited by 200 · cited 9× · see citing works
“In addition, the Ca2+ chelator BAPTA-AM suppresses osteoclast differentiation mediated by RANKL through the inhibition of nuclear localization of NFATc1.”
BackgroundInfluentialKim, Y., Sato, K., Asagiri, M., Morita, I., Soma, K., & Takayanagi, H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505820200 · Cited by 198 · cited 1× · see citing works
“In particular, NFATc1, a master regulator of osteoclast differentiation, regulates a number of osteoclast specific genes such as TRAP, cathepsin K, calcitonin receptor, and osteoclast-associated receptor (OSCAR) through cooperation with MITF and c-Fos.[10-13] The essential role of NFATc1 in osteoclast differentiation…”
BackgroundA Conserved Docking Motif for CK1 Binding Controls the Nuclear Localization of NFAT1
Okamura, H., García‐Rodríguez, C., Martinson, H. M., Qin, J., Virshup, D. M., & Rao, A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.10.4184-4195.2004 · Cited by 188 · cited 1× · see citing works
“Several kinases such as glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), p38, and JNK phosphorylate the various serine-rich motifs in NFAT proteins, thereby preventing translocation into the nucleus or promoting nuclear export of NFAT proteins.[59-63] A recent study has reported that the ectopic expression of…”
BackgroundMicroRNA biogenesis and regulation of bone remodeling
Kapinas, K., & Delany, A. M. (2011) · Arthritis Research & Therapy · doi:10.1186/ar3325 · Cited by 187 · cited 1× · see citing works
“[53,54] The miRNA biogenesis pathway has multiple steps: transcription, pri-miRNA processing, transport to the cytoplasm, precursor miRNA processing, strand selection, target transcription, and fate transcription.[55,56] Very little is known about the role of miRNAs during osteoclast differentiation.”
BackgroundA Role for the p38 MAP Kinase Pathway in the Nuclear Shuttling of NFATp
Arco, P. G., Martı́nez-Martı́nez, S., Maldonado, J. L., Ortega‐Pérez, I., & Redondo, J. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.18.13872 · Cited by 159 · see citing works
MicroRNA-124 regulates osteoclast differentiation
Lee, Y., Kim, H. J., Park, C., Kim, Y., Lee, H., Kim, J., & Kim, H. (2013) · Bone · doi:10.1016/j.bone.2013.07.007 · Cited by 158 · cited 1× · see citing works
“Lee et al.[57] have shown that miRNA-124 regulates osteoclastogenesis by suppressing NFATc1 expression (Fig.”
BackgroundSelf-citationTakatsuna, H., Asagiri, M., Kubota, T., Oka, K., Osada, T., Sugiyama, C., Saito, H., Aoki, K., Ohya, K., Takayanagi, H., et al. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.041213 · Cited by 153 · see citing works
Phosphorylation, acetylation and ubiquitination: The molecular basis of RUNX regulation
Bae, S., & Lee, Y. H. (2005) · Gene · doi:10.1016/j.gene.2005.10.017 · Cited by 147 · cited 1× · see citing works
“Post-translational modification such as ubiquitination and acetylation are important mechanisms of gene regulation.[50] Our previous studies have indicated that the stability of NFATc1 proteins is controlled by ubiquitination and”
BackgroundYasui, T., Hirose, J., Tsutsumi, S., Nakamura, K., Aburatani, H., & Tanaka, S. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.464 · Cited by 126 · cited 1× · see citing works
“[47,48] Yasui et al.[49] recently used ChIP sequencing technology to demonstrate that histone H3 lysine 4 (H3K4me3) is present in the NFATc1 gene in osteoclast precursor cells, but is markedly reduced in mature osteoclasts.”
BackgroundId helix-loop-helix proteins negatively regulate TRANCE-mediated osteoclast differentiation
Lee, J., Kim, K., Kim, J. H., Jin, H. M., Choi, H. K., Lee, S., Kook, H. Y., Kim, K. K., Yokota, Y., Lee, S. Y., et al. (2005) · Blood · doi:10.1182/blood-2005-07-2798 · Cited by 93 · cited 1× · see citing works
“1).[40-42] We have also found that protein inhibitor of activated STAT3 (PIAS3) inhibits RANKL-mediated transcription of NFATc1 (Fig.”
BackgroundSelf-citationInactivation of Glycogen Synthase Kinase-3β Is Required for Osteoclast Differentiation
Jang, H. D., Shin, J. H., Park, D. R., Hong, J. H., Yoon, K., Ko, R., Ko, C., Kim, H. S., Jeong, D., Kim, N., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.256768 · Cited by 84 · see citing works
Self-citationKim, J. H., Kim, K., Youn, B. U., Jin, H. M., Kim, J.-Y., Moon, J. B., Ko, A., Seo, S., Lee, K.-Y., & Kim, N. (2011) · Biochemical Journal · doi:10.1042/bj20110062 · Cited by 79 · cited 8× · see citing works
“In addition, the Ca2+ chelator BAPTA-AM suppresses osteoclast differentiation mediated by RANKL through the inhibition of nuclear localization of NFATc1.”
BackgroundResultInfluentialSelf-citationKim, K., Lee, J., Kim, J. H., Jin, H. M., Zhou, B., Lee, S. Y., & Kim, N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5588 · Cited by 57 · cited 1× · see citing works
“1).[43] Interferon regulatory factor-8 (IRF-8) and B-cell CLL/lymphoma 6 (Bcl-6) have also been identified as negative regulators of NFATc1.”
BackgroundSelf-citationKim, J. H., Kim, K., Jin, H. M., Song, I., Youn, B. U., Lee, S., Choi, Y., & Kim, N. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.042812 · Cited by 52 · see citing works
Self-citationEpigenetic regulation of osteoclast differentiation
Yasui, T., Hirose, J., Aburatani, H., & Tanaka, S. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06245.x · Cited by 50 · cited 1× · see citing works
“These play an important role in the determination of cell fate.[47] Among the epigenetic modification methods, DNA methylation is understood the best.”
Kiani, A., Habermann, I., Haase, M., Feldmann, S., Boxberger, S., Sanchez-Fernandez, M. A., Thiede, C., Bornhäuser, M., & Ehninger, G. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0404259 · Cited by 48 · cited 1× · see citing works
“Since the discovery of the first NFAT protein, NFATs have been discovered to be involved in immune cell activation, heart valve formation, cardiac hypertrophy, and osteoclast development.[16-19] However, the function and regulation of NFAT proteins is best understood in T cells.”
BackgroundLhx2 regulates bone remodeling in mice by modulating RANKL signaling in osteoclasts
Kim, J. H., Youn, B. U., Kim, K., Moon, J. B., Lee, J., Nam, K.-I. I., Park, Y.-W., O'Leary, D. D. M., Kim, K. K., & Kim, N. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2014.71 · Cited by 26 · cited 2× · see citing works
“1).[40-42] We have also found that protein inhibitor of activated STAT3 (PIAS3) inhibits RANKL-mediated transcription of NFATc1 (Fig.”
BackgroundSelf-citation
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Immunology of Osteoporosis: A Mini-Review
Pietschmann, P., Mechtcheriakova, D., Meshcheryakova, A., Föger‐Samwald, U., & Ellinger, I. (2015) · Gerontology · doi:10.1159/000431091 · Cited by 289 · see citing works
Yu, W. H., Zhong, L., Yao, L., Wei, Y., Gui, T., Li, Z., Kim, H., Holdreith, N., Jiang, X., Tong, W., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci140214 · Cited by 213 · see citing works
“Nfatc1, a master regulator of osteoclast differentiation (20), was present within the osteoclast lineage differentiation, supporting the reliability of our computational analysis.”
ResultCommon signalling pathways in macrophage and osteoclast multinucleation
Pereira, M., Petretto, E., Gordon, S., Bassett, J. H. D., Williams, G., & Behmoaras, J. (2018) · Journal of Cell Science · doi:10.1242/jcs.216267 · Cited by 179 · see citing works
“Indeed, in osteoclasts, most studies show that RANK-mediated signalling pathways and/or transcription factors converge towards NFATc1 as the ultimate master regulator of osteoclast multinucleation (Kim and Kim, 2014).”
BackgroundInfluence of Iron on Bone Homeostasis
Balogh, E., Paragh, G., & Jeney, V. (2018) · Pharmaceuticals · doi:10.3390/ph11040107 · Cited by 191 · see citing works
“Among them, NFATc1 is considered to be the master transcription factor that drives terminal differentiation of osteclasts via regulating numerous osteoclast-specific genes such as tartrate-resistant acid phosphatase (TRAP), cathepsin K and calcitonin receptor [12,13].”
BackgroundYou, J., Zhang, Y., & Zhou, Y. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.928799 · Cited by 132 · see citing works
Fusaro, M., Cianciolo, G., Brandi, M. L., Ferrari, S., Nickolas, T. L., Tripepi, G. L., Plebani, M., Zaninotto, M., Iervasi, G., Manna, G. L., et al. (2020) · Nutrients · doi:10.3390/nu12123625 · Cited by 129 · see citing works
“RANKL selectively induces the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), the key transcriptional factor in osteoclastogenesis [41,42] whose nuclear translocation and activation [43,44] is regulated by the activation of calcium-calcineurin pathway [45].”
BackgroundNF-κB as a Therapeutic Target in Inflammatory-Associated Bone Diseases
Lin, T., Pajarinen, J., Lu, L. Y., Nabeshima, A., Córdova, L. A., Yao, Z., & Goodman, S. B. (2016) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2016.11.002 · Cited by 123 · see citing works
“All of these pathways synergize to induce the expression of transcription factor NFATc1 that directly activates the transcription of OC-related genes and is considered as the master regulator of OC formation and sustained function (Kim & Kim, 2014; Takayanagi et al., 2002).”
BackgroundBone Health in Patients with Dyslipidemias: An Underestimated Aspect
Anagnostis, P. G., Florentin, M., Livadas, S., Lambrinoudaki, I. V., & Goulis, D. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031639 · Cited by 114 · see citing works
“RANKL is released by osteoblast lineage cells and binds to RANK, leading to the differentiation of osteoclast precursor cells into mature osteoclasts [96].”
BackgroundLi, P., Dai, J., Li, Y., Alexander, D., Čapek, J., Geis‐Gerstorfer, J., Wan, G., Han, J., Yu, Z., & Li, A. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100932 · Cited by 114 · see citing works
“NFATc1 activity is considered as a master transcription regulator of osteoclastogenesis [77,78].”
BackgroundA catalog of single nucleotide changes distinguishing modern humans from archaic hominins
Kuhlwilm, M., & Boeckx, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-44877-x · Cited by 108 · see citing works
“…genes harboring an excess of HF SNCs associated with specific facial features, we find RUNX2, EDAR, and GLI3 (Adhikari et al. 2016), NFATC1 (Kim and Kim 2014), SPOP (Cai and Liu 2016), DDR2 (Zhang et al. 2011) and NELL1 (Zhang et al. 2012), possibly carrying changes in regulatory regions, while…”
BackgroundBellomo, A., Mondor, I., Spinelli, L., Lagueyrie, M., Stewart, B. J., Brouilly, N., MALISSEN, B., Clatworthy, M. R., & Bajénoff, M. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.008 · Cited by 101 · see citing works
“Inthebone, Nfatc1 regulatesosteoclastdifferentiation(Kim and Kim, 2014) whereas in the liver, Id3 and Lxra control Kupffer cell identity (Bonnardel et al., 2019; Endo-Umeda et al., 2018; Mass et al., 2016; Sakai et al., 2019).”
Long noncoding RNAs: a missing link in osteoporosis
da Silva, A. M., Moura, S. R., Teixeira, J. H., Barbosa, M. A., Santos, S. G., & Almeida, M. I. (2019) · Bone Research · doi:10.1038/s41413-019-0048-9 · Cited by 99 · see citing works
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“In IL-4–polarized macrophages, the expression and activation of both NFATc-1 and c-fos are impaired leading to lower cathepsin K expression and activity.(36,52,53) The fact that CD68MR macrophages accumulate around calcified areas could be the consequence of their incapacity to resorb preexisting calcium phosphate cry…”
BackgroundExperimental infection of warthos (Phacochoerus aethiopicus) with African swine fever virus.
Thomson, G. R., Gainaru, M. D., & van Dellen, A. F. (1980) · PubMed · Cited by 97 · see citing works
RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts
Bae, S., Kim, K., Kang, K., Kim, H., Lee, M. J., Oh, B., Kaneko, K., Ma, S., Choi, J., Kwak, H., et al. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00959-x · Cited by 99 · see citing works
Epigenetic and transcriptional regulation of osteoclast differentiation
Kurotaki, D., Yoshida, H., & Tamura, T. (2020) · Bone · doi:10.1016/j.bone.2020.115471 · Cited by 97 · see citing works
Kim, B., Lee, K. Y., & Park, B. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.06.020 · Cited by 92 · see citing works
Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation
Wei, M., Lu, G., Sha, X., Lu, H., Yinghao, J., Xiaoying, L., Cheng-ming, X., Banjun, R., Li, W., & Lu, Z. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.05.135 · Cited by 94 · see citing works
SIRT2 regulates extracellular vesicle-mediated liver-bone communication
Lin, L., Guo, Z., He, E., Long, X., Wang, D., Zhang, Y., Guo, W., Wei, Q., He, W., Wu, W., et al. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00803-0 · Cited by 88 · see citing works
Tan, E. M., Li, L., Indran, I. R., Chew, N., & Yong, E. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3031 · Cited by 81 · see citing works
“In addition to the NF-kB pathway, NFATc1 expression is regulated by the AP-1 transcription factor, downstream of MAPK, JNK, ERK, and p38.((13)) Indeed, we have shown that ICT inhibited RANKL-induced phosphorylation of JNK, ERK, and p38 and correspondingly downregulated AP-1 transcriptional activity.”
BackgroundInfluentialEffects of Caffeic Acid and Its Derivatives on Bone: A Systematic Review
Ekeuku, S. O., Pang, K. L., & Chin, K. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s287280 · Cited by 77 · see citing works
“NFATc1 is the master regulator of osteoclast-related gene expression, and it is activated by c-Fos and NFκB.(76) Ha et al.”
BackgroundInfluentialMa, Y., & Zhou, X. (2024) · Nature Methods · doi:10.1038/s41592-024-02284-9 · Cited by 77 · see citing works
“C ) related to infiltrating immune systems 31,32 in domain 8, supporting an immune interface at the tumor edge (Fig.”
Osteoclasts, key players in skeletal health and disease
Novack, D., & Mbalaviele, G. (2016) · Microbiology spectrum · doi:10.1128/microbiolspec.mchd-0011-2015 · Cited by 73 · see citing works
“Developing evidence also indicates a crucial role of epigenetic mechanisms in RANKL control of OC differentiation (74, 75).”
BackgroundDeng, W., Ding, Z., Wang, Y., Zou, B., Zheng, J., Tan, Y., Yang, Q. Z., Ke, M., Chen, Y., Wang, S., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153838 · Cited by 73 · see citing works
Doss, H. M., Samarpita, S., Ramamoorthi, G., & Rasool, M. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.06.013 · Cited by 70 · see citing works
Yang, L.-C., Lin, S.-W., Li, I.-C., Chen, Y., Tzu, S.-Y., Chou, W., Chen, C.-C., Lin, W., Chen, Y., & Lin, W. (2020) · Nutrients · doi:10.3390/nu12071914 · Cited by 68 · see citing works
de Molon, R. S., Vernal, R., Oliveira, G. E., Steffens, J. P., Ervolino, E., Theodoro, L. H., van den Beucken, J. J. J. P., & Tetradis, S. (2026) · Bone Research · doi:10.1038/s41413-025-00478-1 · Cited by 83 · see citing works
Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation
Yi, S.-J., Lee, H.-R., Lee, J., Lee, K., Kim, J., Kim, Y., Park, J., & Kim, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133147 · Cited by 68 · see citing works
“The binding of RANKL to RANK receptor results in the recruitment of tumor necrosis factor receptor-associated factor 6 (TRAF6), which in turn activates diverse signaling pathways such as nuclear factor kappa B (NF-κB), c-JUN N-terminal kinase (JNK), p38 mitogen-activated protein kinase, and extracellular signal-relate…”
BackgroundSelf-citationLong noncoding RNA Malat1 protects against osteoporosis and bone metastasis
Zhao, Y., Ning, J., Teng, H., Deng, Y., Sheldon, M., Shi, L., Martinez, C., Zhang, J., Tian, A., Sun, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46602-3 · Cited by 68 · see citing works
“Besides TEAD, our Mentha database search also revealed other candidate NFATC1-interacting proteins, among which FOS, JUN, and CREB1 have been reported to regulate osteoclast differentiation 57,58 (Supplementary Fig.”
BackgroundMelatonin, bone regulation and the ubiquitin-proteasome connection: A review
Vriend, J. P., & Reiter, R. J. (2015) · Life Sciences · doi:10.1016/j.lfs.2015.12.031 · Cited by 66 · see citing works
“Amajor regulator of osteoclast formation is the protein NFATc1 (nuclear factor of activated T cells) which interacts with NF-κB as a transcription factor [2,55,117].”
BackgroundBioactive effects of silica nanoparticles on bone cells are size, surface, and composition dependent
Ha, S., Viggeswarapu, M., Habib, M. M., & Beck, G. R. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.10.018 · Cited by 66 · see citing works
Pang, M., Rodríguez‐Gonzalez, M., Hernandez, M., Recinos, C. C., Seldeen, K. L., & Troen, B. R. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28504 · Cited by 66 · see citing works
Yang, J.-G., Sun, B., Wang, Z., Li, X., Gao, J.-H., Qian, J., Li, J., Wei, W.-J., Zhang, P., & Wang, W. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06263-4 · Cited by 66 · see citing works
Kim, H., Walsh, M. C., Takegahara, N., Middleton, S. A., Shin, H., Kim, J., & Choi, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-00139-2 · Cited by 65 · see citing works
“At the same time, temporal analyses of protein expression in P2rx5 + / + and P2rx5 − / − lysates prepared from OC cultures showed that while P2X5 expression peaks in P2rx5 + / + cells at day three of RANKL treatment, critical OC differentiation and maturation factors NFATc1 29 , c-Src 30 , and Atp6v0d2 31 (Fig.”
InfluentialSelf-citationNeog, M. K., Pragasam, S. J., Krishnan, M., & Rasool, M. (2017) · BioFactors · doi:10.1002/biof.1377 · Cited by 65 · see citing works
“Moreover, diminished expression of MAPK (JNK and ERK1/2), NF-jB, NFATc1, and c-Fos with attenuated RANKL expression in AIA could have inhibited the further differentiation of osteoclast [13].”
BackgroundEffects of hydroxyapatite surface nano/micro-structure on osteoclast formation and activity
Chen, F., Wang, M., Wang, J., Chen, X., Li, X., Xiao, Y., & Zhang, X. (2019) · Journal of Materials Chemistry B · doi:10.1039/c9tb01204d · Cited by 64 · see citing works
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“Therefore, the cytokines M-CSF and RANKL play a crucial role in osteoclast differentiation by respectively inducing ubiquitination and acetylation of NFATc1, which regulates its stability and activity (Kim and Kim 2014).”
BackgroundHealth benefits of flaxseed and its peptides (linusorbs)
Shim, Y. Y., Kim, J. H., Cho, J. Y., & Reaney, M. J. T. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2119363 · Cited by 62 · see citing works
“Sequentially, RANKL, primarily expressed by osteoblast cells, activates the RANK on osteoclast pre-cursors, and nuclear factor of activated T cells 1 (NFATc1), a master regulator of osteoclastogenesis, is activated via c-fos (Kim and Kim 2014; Yavropoulou and Yovos 2008).”
BackgroundSelf-citationYAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism
Zhao, L., Guan, H., Song, C., Wang, Y., Liu, C. Y., Cai, C., Liu, H., Liu, H., Zhao, L., & Xiao, J. (2018) · Bone · doi:10.1016/j.bone.2018.01.035 · Cited by 62 · see citing works
Neog, M. K., & Rasool, M. (2018) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2018.10.010 · Cited by 62 · see citing works
Osteoclasts Differentiation from Murine RAW 264.7 Cells Stimulated by RANKL: Timing and Behavior
Lampiasi, N., Russo, R., Kireev, I. I., Strelkova, O. S., Zhironkina, O. A., & Zito, F. (2021) · Biology · doi:10.3390/biology10020117 · Cited by 59 · see citing works
“During OC differentiation, NFATc1 translocates to the nucleus and activates both OC-specific genes and its own transcription [26].”
BackgroundCalycosin Suppresses RANKL-Mediated Osteoclastogenesis through Inhibition of MAPKs and NF-κB
Quan, G.-H., Wang, H., Cao, J., Zhang, Y., Wu, D., Peng, Q., Liu, N., & Sun, W. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161226179 · Cited by 58 · see citing works
“MMP-9, through cooperation with MITF and c-Fos [28].”
BackgroundKim, J., Kim, M., Jung, H., & Sohn, Y. (2019) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2019.4269 · Cited by 57 · see citing works
“As LS strongly inhibited NFATc1, it can thus be hypothesized that LS may also suppress the expression of NFATc1-regulated osteoclast-associated genes, including TRAP, MMP-9, ctsk, ATP6v0d2 and OScAR (9).”
BackgroundInfluentialSelf-citationQiu, C., Yu, F., Su, K., Zhao, Q., Zhang, L., Xu, C., Hu, W., Wang, Z., Zhao, L., Tian, Q., et al. (2020) · iScience · doi:10.1016/j.isci.2020.100847 · Cited by 53 · see citing works
“…a ubiquitous TF in many cell types, is a well-known master regulator of both osteoblastogenesis and osteoclastogenesis (Fromigue et al., 2010; Kim and Kim, 2014) and has been demonstrated to play crucial roles in regulating bone homeostasis and bone mass (Winslow et al., 2006; Lee et al., 2009).”
BackgroundLi, S.-F., Yang, B., Teguh, D., Zhou, L., Xu, J.-K., & Rong, L. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101683 · Cited by 49 · see citing works
“NFATc1, whose overexpression can drive OC formation independently of RANKL, is a critical transcription factor which is essential for osteoclastogenesis [28].”
BackgroundReduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK
Wang, C., He, H., Wang, L., Jiang, Y. Y., & Xu, Y. (2018) · Biochemistry and Cell Biology · doi:10.1139/bcb-2017-0243 · Cited by 53 · see citing works
“NFATC1 is involved in the NFATC1 382 signalling pathway, which is critical to the regulation of osteoclast differentiation and 383 maturation (CROTTI et al. 2006; KIM and KIM 2014).”
BackgroundZhao, H., Zhao, N., Zheng, P., Xu, X., Liu, M., Luo, D., Xu, H., & Ju, D. (2018) · Journal of Immunology Research · doi:10.1155/2018/6345857 · Cited by 53 · see citing works
“RANKLRANK interaction activates the master transcription factor for osteoclastogenesis; nuclear factor of activated T cells, cytoplasmic 1 (NFATc1); tartrate-resistant acid phosphatase; calcitonin receptor; and cathepsin K [27].”
BackgroundMEF2C regulates osteoclastogenesis and pathologic bone resorption via c-FOS
Fujii, T., Murata, K., Mun, S. H., Bae, S., Lee, Y. J., Pannellini, T., Kang, K., Oliver, D., Park‐Min, K., & Ivashkiv, L. B. (2021) · Bone Research · doi:10.1038/s41413-020-00120-2 · Cited by 53 · see citing works
Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
“NFATc1 binds to its own promoter, switching on an epigenetically controlled autoregulatory cycle that permits efficient induction of the osteoclast-specific genes, tartrate-resistant acid phosphatase (TRAP), cathepsin K, as well as the fusion-specific genes, dendritic cell-specific transmembrane protein (DC-STAMP) and…”
BackgroundBCAT1 promotes osteoclast maturation by regulating branched-chain amino acid metabolism
Go, M., Shin, E.-J., Jang, S. Y., Nam, M., Hwang, G., & Lee, S. Y. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00775-3 · Cited by 50 · see citing works
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MicroRNAs: Key Regulators to Understand Osteoclast Differentiation?
Lozano, C., Duroux-Richard, I., Firat, H., Schordan, E., & Apparailly, F. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00375 · Cited by 50 · see citing works
Nrf2 Mitigates RANKL and M-CSF Induced Osteoclast Differentiation via ROS-Dependent Mechanisms
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“The interaction between c-FOS and the promoter region of NFATc1 leads to the activation of the NFATc1 gene [8], which is a key regulator of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP), H + -ATPase, Atp6v0d2, Oscar, and Cathepsin K marker genes [9].”
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“Activated AKT inhibits GSK-3β, which subsequently downregulates NFATc1 expression [76,77], and this reduces osteoclast differentiation [78].”
BackgroundRegulation of differentiation and generation of osteoclasts in rheumatoid arthritis
Niu, Q., Gao, J., Wang, L., Liu, J., & Zhang, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1034050 · Cited by 49 · see citing works
“RANKL regulates the activation of NFATcl and promotes the differentiation of OC through two signal pathways: NF- k B/AP-1/c-fos and calcium signal pathway (20).”
BackgroundDual Role of Cyanidin-3-glucoside on the Differentiation of Bone Cells
Park, K.-H., Gu, D. R., So, H., Kim, K. J., & Lee, S. H. (2015) · Journal of Dental Research · doi:10.1177/0022034515604620 · Cited by 46 · see citing works
“In addition, the RANKL-RANK interaction induces the expression of transcription factors, including nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis both in vitro and in vivo (Takayanagi 2007; Kim and Kim 2014).”
BackgroundJMJD3: a critical epigenetic regulator in stem cell fate
Ding, Y., Yao, Y., Gong, X., Zhuo, Q., Chen, J., Tian, M., & Farzaneh, M. (2021) · Cell Communication and Signaling · doi:10.1186/s12964-021-00753-8 · Cited by 45 · see citing works
The Multiple Roles of Microrna-223 in Regulating Bone Metabolism
Xie, Y., Zhang, L., Gao, Y., Ge, W., & Tang, P. (2015) · Molecules · doi:10.3390/molecules201019433 · Cited by 45 · see citing works
“RelB/p52 heterodimers can translocate to the nucleus to induce nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) [61], which is necessary for osteoclast”
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Transcriptional Regulation of Osteoclastogenesis: The Emerging Role of KLF2
Rolph, D. N., & Das, H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00937 · Cited by 44 · see citing works
“Intermediate signals downstream of TRAF6 are mediated via NF-κB and c-Fos (Figure 2) (45).”
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Mustafa, N. H., Sekar, M., Fuloria, S., Begum, M. Y., Gan, S. H., Rani, N. N. I. M., Ravi, S., Chidambaram, K., Subramaniyan, V., Sathasivam, K. V., et al. (2022) · Molecules · doi:10.3390/molecules27062032 · Cited by 44 · see citing works
Microbiota metabolites in bone: Shaping health and Confronting disease
Han, D., Wang, W., Gong, J., Ma, Y., & Li, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e28435 · Cited by 44 · see citing works
“This transcription factor is essential for osteoclast cell growth and is thought to be found in the nucleus of osteoclast progenitors [207,208].”
BackgroundCircadian Regulation of Bone Remodeling
Kikyo, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094717 · Cited by 42 · see citing works
“NFATc1 activates many osteoclast-specific genes, including cathepsin K ( Ctsk ), tartrate-resistant acid phosphatase 5 ( Trap or Acp5 , a marker protein widely used to detect osteoclasts via enzyme histochemistry), and calcitonin receptor ( Calcr ) [41].”
BackgroundWang, Q., Yao, L., Ke Cheng, X. U., Jin, H., Chen, K., Wang, Z., Liu, Q., Cao, Z., Kenny, J., Liu, Y., et al. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13942 · Cited by 42 · see citing works
“Therefore, we propose that MA can regulate the activation of AP‐1 F IGURE 10 A schematic diagram helps in understanding the role of Madecassoside in suppressing RANKL‐ induced osteoclastogenesis by interfering with MAPK signaling and inhibiting the subsequent induction of NFATc1.”
BackgroundInfluentialRaimondi, L., Luca, A. D., Fontana, S., Amodio, N., Costa, V., Carina, V., Bellavia, D., Raimondo, S., Siragusa, S. M., Monteleone, F., et al. (2020) · Cancers · doi:10.3390/cancers12082167 · Cited by 43 · see citing works
The hidden secrets of soluble RANKL in bone biology
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AMPK negatively regulates RANKL-induced osteoclast differentiation by controlling oxidative stress
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Periodontal materials and cell biology for guided tissue and bone regeneration
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Pathogenesis of Periodontal Disease
Muñoz‐Carrillo, J. L., Hernández-Reyes, V. E., García-Huerta, O. E., Chávez-Ruvalcaba, F., Chávez-Ruvalcaba, M. I., Chávez-Ruvalcaba, K. M., & Díaz-Alfaro, L. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.86548 · Cited by 41 · see citing works
“RANKL is a cytokine member of the TNF family that can be bound or secreted to the membrane and stimulates the differentiation of osteoclasts, cell fusion, and activation that leads to bone resorption [40, 41].”
BackgroundAllison, H., & McNamara, L. M. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00168.2019 · Cited by 41 · see citing works
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Directed Differentiation of Human Induced Pluripotent Stem Cells to Heart Valve Cells
Cai, Z., Zhu, M., Xu, L., Wang, Y., Xu, Y., Yim, W. Y., Cao, H., Guo, R., Qiu, X., He, X., et al. (2024) · Circulation · doi:10.1161/circulationaha.123.065143 · Cited by 40 · see citing works
“33,34 Therefore, we selected 3 different Ca 2+ channel activators (forskolin, Bay K 8644, and FPL 64176) or RANKL combined with VEGF-165 to promote the differentiation of heart valve cells from hiCLPM.”
MethodKwak, S. C., Baek, J. M., Lee, C. H., Yoon, K., Lee, M. S., & Kim, J. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.28609 · Cited by 40 · see citing works
“These two distinct signaling pathways activate nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is a key transcription regulator of osteoclast differentiation, inducing the release of a number of osteoclast-specific genes, such as tartrate-resistant acid phosphatase (TRAP), osteoclast-associated recep…”
BackgroundSelf-citationLiu, W.-C., Shyu, J., Lim, P., Fang, T., Lu, C., Zheng, C., Hou, Y., Wu, C., Lin, Y., & Lu, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103486 · Cited by 40 · see citing works
“The nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), one of AhR target proteins, plays an important role in osteoclast precursor differentiation [16] and is a major transcription factor for osteoclastogenesis [17].”
BackgroundHairi, H. A., Jayusman, P. A., & Shuid, A. N. (2023) · Biomedicines · doi:10.3390/biomedicines11051453 · Cited by 39 · see citing works
Endoplasmic Reticulum–Bound Transcription Factor CREBH Stimulates RANKL-Induced Osteoclastogenesis
Kim, J. H., Kim, K., Kim, I., Seong, S., Kim, K. K., Kim, N., & Kim, N. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701036 · Cited by 39 · see citing works
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The KDM4B–CCAR1–MED1 axis is a critical regulator of osteoclast differentiation and bone homeostasis
Yi, S.-J., Jang, Y.-J., Kim, H., Lee, K., Lee, H.-R., Kim, Y., Kim, J., Hwang, S. Y., Song, J. S., Okada, H., et al. (2021) · Bone Research · doi:10.1038/s41413-021-00145-1 · Cited by 39 · see citing works
“NT (1-660) CT (661-1 146) SAP Coiled-coil (792-819)”
Self-citationJeong, B., Kim, J. H., Kim, K., Kim, I., Seong, S., & Kim, N. (2016) · Bone · doi:10.1016/j.bone.2016.11.005 · Cited by 38 · see citing works
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“NFATc1 is a critical transcription factor in promoting RANKL-induced osteoclastogenesis by activating the transcription of genes involved in osteoclast differentiation and activity [21].”
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Choo, Y.-Y., Trần, P. T., Min, B.-S., Kim, O., Nguyen, H. D., Kwon, S., & Lee, J. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.09.018 · Cited by 36 · see citing works
Development of PEI- RANK siRNA Complex Loaded PLGA Nanocapsules for the Treatment of Osteoporosis
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“9 It regulates the expression of osteoclast specific genes such as tartrate resistant acid phosphatase ( TRAP ), Cathepsin K, and calcitonin receptor, 9,10 and therefore, osteoclastic differentiation is initiated (Fig.”
Toxic Effects of Indoxyl Sulfate on Osteoclastogenesis and Osteoblastogenesis
Shyu, J., Liu, W.-C., Zheng, C., Fang, T., Hou, Y., Chang, C., Liao, T.-Y., Chen, Y.-C., & Lu, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222011265 · Cited by 36 · see citing works
“In the differentiation stage of osteoclast precursors, the nuclear factor of activated cytoplasmic T lymphocytes 1 (NFATc1) plays a dominant role [111].”
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“NFATc1 can also activate the expression of genes that typify the osteoclast lineage including CTSK, MMP9, and TRAP, leading to the eventual formation of mature osteoclasts [5, 40].”
BackgroundSrivastava, S., & Rasool, M. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123075 · Cited by 34 · see citing works
STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced osteoclastogenesis
Lee, J., Seong, S., Kim, J. H., Kim, K., Kim, I., Jeong, B., Nam, K. I., Kim, K. K., Hennighausen, L. G., & Kim, N. (2016) · Scientific Reports · doi:10.1038/srep30977 · Cited by 34 · see citing works
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“Furthermore, we explored whether the expression of nuclear factor of activated T-cells 1 (NFATc1), a master regulator gene that is upregulated by RANKL, was affected by IL-7 during osteoclastogenesis because RANKL upregulates NFATc1 via the expression of the early osteoclastic gene, c-Fos, which, in turn, induces oste…”
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Florczyk, U., Józefczuk, E., Stępniewski, J., Bukowska-Straková, K., Mendel, M., Viscardi, M., Nowak, W. N., Józkowicz, A., & Dulak, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-29122-1 · Cited by 33 · see citing works
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“Interestingly, loss of Acer1 did not reduce the expression of the Sox9, Nfatc1, and Lgr5 in HFSCs (Figure S6B), although these genes are known downstream targets of Lhx2 (Kim and Kim, 2014; Kim et al., 2014; Mardaryev et al., 2011), suggesting that loss of Acer1 reduces HFSC quiescence through an unknown target(s) of…”
InfluentialHwang, Y., Ha, H., 김라정, Cho, C., Song, Y., Hong, H., & Kim, T. S. (2018) · Nutrients · doi:10.3390/nu10070901 · Cited by 32 · see citing works
“RANKL binding to its receptor RANK initially activates both the MAPK and NF-κB pathways, which are essential signal pathways in the formation, activation, and survival of osteoclasts [33].”
BackgroundInfluentialCurrent perspectives of osteoclastogenesis through estrogen modulated immune cell cytokines
Uehara, I. A., Soldi, L. R., & Silva, M. J. B. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117921 · Cited by 34 · see citing works
- Authors
- Kim, J. H., & Kim, N.
- Affiliations
- Chonnam National University (KR)
- Corresponding author
- Kim, Nacksung
- Venue
- Journal of Bone Metabolism
- Published
- 2014
- Volume
- 21
- Issue
- 4
- Pages
- 233
- ISSN
- 2287-6375 (ISSN-L)
- 2287-7029
- PMC
- PMC4255043
- OpenAlex
- W2132541910
- Cited by
- 570
- References
- 69
- Citations by year
- 2026: 54 · 2025: 43 · 2024: 54 · 2023: 64 · 2022: 58 · 2021: 57 · 2020: 68 · 2019: 51 · 2018: 46 · 2017: 31 · 2016: 26 · 2015: 17
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Bone Metabolism (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- NFATc1, osteoclastogenesis, transcriptional regulation, epigenetic regulation, DNA methylation, ubiquitination, acetylation, non-coding RNA, macrophage colony-stimulating factor, RANKL, MITF, c-fos, NF-κB, bone resorption
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