Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro
Open accessAbstract
Fatigue loading causes a spatial distribution of osteocyte apoptosis co‐localized with bone resorption spaces peaking around microdamage sites. Since osteocytes have been shown to regulate osteoclast formation and activity, we hypothesize that osteocyte apoptosis regulates osteoclastogenesis. In this study, we used serum‐starvation to mimic reduced nutrient transport in microdamaged bone and induce apoptosis in MLO‐Y4 osteocyte‐like cells; conditioned medium was used to apply soluble factors released by apoptotic osteocytes (aOCY) to healthy non‐apoptotic MLO‐Y4 cells. Osteoclast precursor (RAW264.7 monocyte) migration and differentiation were assessed in the presence of conditioned media (CM) from: (A) aOCY, (B) osteocytes treated with apoptosis conditioned medium (i.e., healthy osteocytes in the presence of apoptosis cues; apoptosis CM‐treated osteocytes (atOCY)), and (C) osteocytes treated with non‐apoptosis conditioned medium (i.e., healthy osteocytes in the absence of apoptosis cues; non‐apoptosis CM‐treated osteocytes (natOCY)). Receptor activator for nuclear factor‐κB ligand (RANKL), macrophage colony stimulating factor (M‐CSF), vascular endothelial growth factor (VEGF) and osteoprotegerin (OPG) mRNA, and protein expression were measured. Our findings indicate that soluble factors released by aOCY and atOCY promoted osteoclast precursor migration (up to 64% and 24% increase, respectively) and osteoclast formation (up to 450% and 265% increase, respectively). Osteoclast size increased up to 233% in the presence of aOCY and atOCY CM. Recruitment, formation and size were unaltered by natOCY. RANKL mRNA and protein expression were upregulated only in aOCY, while M‐CSF and VEGF increased in atOCY. Addition of RANKL‐blocking antibody abolished aOCY‐induced osteoclast precursor migration and osteoclast formation. VEGF and M‐CSF blocking antibodies abolished atOCY‐induced osteoclastogenesis. These findings suggest that aOCY directly and indirectly (through atOCY) initiate targeted bone resorption by regulating osteoclast precursor recruitment and differentiation. J. Cell. Biochem. 112: 2412–2423, 2011. © 2011 Wiley‐Liss, Inc.
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Conditioned media of apoptotic MLO-Y4 cells increased osteoclast formation, osteoclast size and osteoclast precursor migration; in apoptotic MLO-Y4 cells, both RANKL mRNA and protein expression were upregulated, suggesting that the conditioned media might contain sRANKL.
“In a different study, the conditioned media of apoptotic MLO-Y4 cells increased osteoclast formation, osteoclast size and osteoclast precursor migration. Interestingly, in apoptotic MLO-Y4 cells, both RANKL mRNA and protein expression were upregulated, suggesting that the conditioned media of this cell culture might contain sRANKL.56”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [56]
Conditioned media of a non-apoptotic MLO-Y4 culture did not alter osteoclast formation, size or precursor migration.
“On the other hand, the conditioned media of a non apoptotic MLO-Y4 culture did not alter any of these aforementioned cell parameters.56”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [56]
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Apoptosis: controlled demolition at the cellular level
Taylor, R. C., Cullen, S. P., & Martin, S. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2312 · Cited by 2,617 · see citing works
Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells
Fink, S. L., & Cookson, B. T. (2005) · Infection and Immunity · doi:10.1128/iai.73.4.1907-1916.2005 · Cited by 2,206 · see citing works
Barleon, B., Sozzani, S., Zhou, D., Weich, H., Mantovani, A., & Marmé, D. (1996) · Blood · doi:10.1182/blood.v87.8.3336.bloodjournal8783336 · Cited by 1,350 · see citing works
Parfitt, A. M. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550303 · Cited by 1,001 · see citing works
Biology of RANK, RANKL, and osteoprotegerin
Boyce, B. F., & Xing, L. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2165 · Cited by 962 · see citing works
Verborgt, O., Gibson, G. J., & Schaffler, M. B. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.1.60 · Cited by 731 · see citing works
Aguirre, J. I., Plotkin, L. I., Stewart, S. A., Weinstein, R. S., Parfitt, A. M., Manolagas, S. C., & Bellido, T. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060107 · Cited by 494 · see citing works
Osteocytes, strain detection, bone modeling and remodeling
Lanyon, L. E. (1993) · Calcified Tissue International · doi:10.1007/bf01673415 · Cited by 439 · see citing works
The CASBAH: a searchable database of caspase substrates
Lüthi, A. U., & Martin, S. J. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402103 · Cited by 434 · see citing works
Noble, B., Peet, N. M., Stevens, H. Y., Brabbs, A. C., Mosley, J. R., Reilly, G. C., REEVE, J., Skerry, T. M., & Lanyon, L. E. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00234.2002 · Cited by 381 · see citing works
Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading
You, L., Temiyasathit, S., Lee, P., Kim, C. H., Tummala, P., Yao, W., Kingery, W. S., Malone, A. M. D., Kwon, R. Y., & Jacobs, C. R. (2007) · Bone · doi:10.1016/j.bone.2007.09.047 · Cited by 361 · see citing works
Self-citationOsteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue
Cardoso, L., Herman, B. C., Verborgt, O., Laudier, D., Majeska, R. J., & Schaffler, M. B. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081210 · Cited by 340 · see citing works
Mechanosensation and transduction in osteocytes
Bonewald, L. F. (2006) · BoneKEy-Osteovision · doi:10.1138/20060233 · Cited by 283 · see citing works
Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo
Axmann, R., Böhm, C., Krönke, G., Zwerina, J., Smolen, J., & Schett, G. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24781 · Cited by 263 · see citing works
Dias, S., Shmelkov, S. V., Lam, G. F. M., & Rafii, S. (2002) · Blood · doi:10.1182/blood.v99.7.2532 · Cited by 259 · see citing works
Phagocytic docking without shocking
Savill, J. (1998) · Nature · doi:10.1038/33025 · Cited by 238 · see citing works
Hikita, A., Yana, I., Wakeyama, H., Nakamura, M., Kadono, Y., Oshima, Y., Nakamura, K., Seiki, M., & Tanaka, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606656200 · Cited by 236 · see citing works
Clemens, M. J., Bushell, M., Jeffrey, I. W., Pain, V. M., & Morley, S. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400695 · Cited by 228 · see citing works
Ikeda, T., Kasai, M., Utsuyama, M., & Hirokawa, K. (2001) · Endocrinology · doi:10.1210/endo.142.4.8070 · Cited by 215 · see citing works
Verborgt, O., Tatton, N. A., Majeska, R. J., & Schaffler, M. B. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.5.907 · Cited by 192 · see citing works
Effect of low-magnitude, high-frequency vibration on osteocytes in the regulation of osteoclasts
Lau, E., Al‐Dujaili, S. A., Günther, A., Liu, D., Wang, L., & You, L. (2010) · Bone · doi:10.1016/j.bone.2010.02.031 · Cited by 190 · see citing works
Self-citationShear stress inhibits while disuse promotes osteocyte apoptosis
Bakker, A. D., Klein‐Nulend, J., & Burger, E. H. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.06.056 · Cited by 185 · see citing works
Henriksen, K., Karsdal, M. A., Delaissé, J., & Engsig, M. T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309193200 · Cited by 157 · see citing works
YANG, Q., McHugh, K. P., Patntirapong, S., GU, X., Wunderlich, L., & Hauschka, P. V. (2008) · Matrix Biology · doi:10.1016/j.matbio.2008.06.005 · Cited by 144 · see citing works
RANKL-Mediated Osteoclast Formation from Murine RAW 264.7 Cells
Collin‐Osdoby, P., Yu, X., Zheng, H., & Osdoby, P. (2003) · Humana Press eBooks · doi:10.1385/1-59259-366-6:153 · Cited by 135 · see citing works
Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption
Gu, G., Mulari, M., Peng, Z., Hentunen, T. A., & Väänänen, H. K. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.06.211 · Cited by 123 · see citing works
Gooi, J. H., Pompolo, S., Karsdal, M. A., Kulkarni, N. H., Kalajzic, I., McAhren, S. H. M., Han, B., Onyia, J. E., Ho, P. W. M., Gillespie, M. T., et al. (2010) · Bone · doi:10.1016/j.bone.2010.02.018 · Cited by 117 · see citing works
Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis
Kogianni, G., Mann, V., Ebetino, F. H., NUTTALL, M. E., Nijweide, P. J., Simpson, H., & Noble, B. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.04.048 · Cited by 110 · see citing works
Vascular endothelial growth factor receptors in osteoclast differentiation and function
Aldridge, S., Lennard, T. W. J., Williams, J. R., & Birch, M. A. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.07.145 · Cited by 104 · see citing works
Street, J., & Lenehan, B. J. (2009) · Journal of Orthopaedic Surgery and Research · doi:10.1186/1749-799x-4-19 · Cited by 102 · see citing works
The Role of Interstitial Fluid Flow in the Remodeling Response to Fatigue Loading
Tami, A., Nasser, P. R., Verborgt, O., Schaffler, M. B., & Tate, M. L. K. (2002) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2002.17.11.2030 · Cited by 97 · see citing works
Fluid Shear Stress Inhibits TNFα-induced Osteocyte Apoptosis
Tan, S., Kuijpers‐Jagtman, A. M., Semeins, C. M., Bronckers, A. L. J. J., Maltha, J. C., den Hoff, J. W. V., Everts, V. E., & Klein‐Nulend, J. (2006) · Journal of Dental Research · doi:10.1177/154405910608501006 · Cited by 86 · see citing works
Mechanisms governing the control of mRNA translation
Livingstone, M., Atas, E., Meller, A., & Sonenberg, N. (2010) · Physical Biology · doi:10.1088/1478-3975/7/2/021001 · Cited by 85 · see citing works
Inhibition of osteoblast apoptosis by thrombin
Pagel, C. N., de Niese, M. R., Abraham, L. A., Chinni, C., Song, S., Pike, R. N., & Mackie, E. J. (2003) · Bone · doi:10.1016/s8756-3282(03)00209-6 · Cited by 75 · see citing works
Microcracks in cortical bone: How do they affect bone biology?
O’Brien, F. J., Brennan, O., Kennedy, O. D., & Lee, T. C. (2005) · Current Osteoporosis Reports · doi:10.1007/s11914-005-0002-1 · Cited by 70 · see citing works
IL-12 inhibits TNF-α induced osteoclastogenesis via a T cell-independent mechanism in vivo
Yoshimatsu, M., Kitaura, H., Fujimura, Y., Eguchi, T., Kohara, H., Morita, Y., & Yoshida, N. (2009) · Bone · doi:10.1016/j.bone.2009.07.079 · Cited by 60 · see citing works
Taylor, D. M., Hazenberg, J. G., & Lee, T. C. (2003) · Journal of Theoretical Biology · doi:10.1016/s0022-5193(03)00222-4 · Cited by 57 · see citing works
Boudot, C., Saidak, Z., Boulanouar, A. K., Petit, L., Gouilleux, F., Massy, Z. A., Brazier, M., Mentaverri, R., & Kamel, S. (2010) · Bone · doi:10.1016/j.bone.2010.01.383 · Cited by 56 · see citing works
Noble, B. (2005) · European Journal of Morphology · doi:10.1080/09243860500096248 · Cited by 43 · see citing works
Yao, S., Liu, D., Pan, F., & Wise, G. E. (2006) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2005.12.006 · Cited by 41 · see citing works
Osteocyte Apoptosis and Osteoclast Presence in Chicken Radii 0–4 Days Following Osteotomy
Clark, W. D., Smith, E. L., Linn, K. A., Paul‐Murphy, J., Muir, P., & COOK, M. E. (2005) · Calcified Tissue International · doi:10.1007/s00223-005-0074-z · Cited by 41 · see citing works
Endostatin inhibits VEGF-A induced osteoclastic bone resorption in vitro
Sipola, A., Nelo, K., Hautala, T., Ilvesaro, J. M., & Tuukkanen, J. (2006) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-7-56 · Cited by 40 · see citing works
ARF Suppresses Tumor Angiogenesis through Translational Control of VEGFA mRNA
Kawagishi, H., Nakamura, H., Maruyama, M., Mizutani, S., Sugimoto, K., Takagi, M., & Sugimoto, M. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0368 · Cited by 39 · see citing works
Hydrogen Peroxide Induces Apoptosis of Osteocytes: Involvement of Calcium Ion and Caspase Activity
Kikuyama, A., Fukuda, K., Mori, S., Okada, M., Yamaguchi, H., & Hamanishi, C. (2002) · Calcified Tissue International · doi:10.1007/s00223-001-1110-2 · Cited by 35 · see citing works
Caldwell, J., Locey, B. J., Clarke, M. F., Emerson, S. G., & Palsson, B. Ø. (1991) · Biotechnology Progress · doi:10.1021/bp00007a001 · Cited by 23 · see citing works
Deng, P., Rettenmier, C. W., Pattengale, P. K., Rettenmier, C. W., & Rettenmier, C. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.27.16338 · Cited by 22 · see citing works
Shibata, H., Abe, M., Hiura, K., Wilde, J., Moriyama, K., Sano, T., Kitazoe, K.-I., Hashimoto, T., Ozaki, S., Wakatsuki, S., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0181 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Osteocyte: An Endocrine Cell … and More
Dallas, S. L., Prideaux, M., & Bonewald, L. F. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1026 · Cited by 1,042 · see citing works
Oxidative stress in bone remodeling: role of antioxidants
Domazetovic, V (2017) · Clinical Cases in Mineral and Bone Metabolism · doi:10.11138/ccmbm/2017.14.1.209 · Cited by 758 · see citing works
Osteocytes: master orchestrators of bone
Schaffler, M. B., Cheung, W.-Y., Majeska, R., & Kennedy, O. (2014) · Calcified Tissue International · doi:10.1007/s00223-013-9790-y · Cited by 514 · see citing works
Bone remodeling: an operational process ensuring survival and bone mechanical competence
Bolamperti, S., Villa, I., & Rubinacci, A. (2022) · Bone Research · doi:10.1038/s41413-022-00219-8 · Cited by 482 · see citing works
Osteoblast and osteocyte: Games without frontiers
Capulli, M., Paone, R., & Rucci, N. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.05.003 · Cited by 413 · see citing works
Oxidative Stress and Osteoporosis
Kimball, J. S., Johnson, J. P., & Carlson, D. A. (2021) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.20.00989 · Cited by 315 · see citing works
Osteocyte RANKL: New insights into the control of bone remodeling
Xiong, J., & O’Brien, C. A. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1547 · Cited by 287 · see citing works
Kennedy, O. D., Herman, B. C., Laudier, D. M., Majeska, R. J., Sun, H. B., & Schaffler, M. B. (2012) · Bone · doi:10.1016/j.bone.2012.01.025 · Cited by 275 · see citing works
“as an anti-apoptotic response to microdamage [18,47,48].”
Riegger, J., Schoppa, A., Ruths, L., Haffner‐Luntzer, M., & Ignatius, A. A. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00489-y · Cited by 255 · see citing works
Schaffler, M. B., & Kennedy, O. D. (2012) · Current Osteoporosis Reports · doi:10.1007/s11914-012-0105-4 · Cited by 227 · see citing works
In vitro models for the study of osteoarthritis
Johnson, C. I., Argyle, D. J., & Clements, D. N. (2015) · The Veterinary Journal · doi:10.1016/j.tvjl.2015.07.011 · Cited by 221 · see citing works
Delgado‐Calle, J., Anderson, J. L., Cregor, M. D., Hiasa, M., Chirgwin, J. M., Carlesso, N., Yoneda, T., Mohammad, K. S., Plotkin, L. I., Roodman, G. D., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1703 · Cited by 214 · see citing works
Zuckerman, P. C., Frikha-Benayed, D., Majeska, R. J., Tuthill, A., Yakar, S., Judex, S., & Schaffler, M. B. (2016) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2807 · Cited by 189 · see citing works
Osteocyte regulation of bone mineral: a little give and take
Atkins, G. J., & Findlay, D. M. (2012) · Osteoporosis International · doi:10.1007/s00198-012-1915-z · Cited by 185 · see citing works
Marcucci, G., Domazetovic, V., Nediani, C., Ruzzolini, J., Favre, C., & Brandi, M. L. (2023) · Antioxidants · doi:10.3390/antiox12020373 · Cited by 191 · see citing works
Kennedy, O. D., Laudier, D. M., Majeska, R. J., Sun, H. B., & Schaffler, M. B. (2014) · Bone · doi:10.1016/j.bone.2014.03.049 · Cited by 151 · see citing works
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 149 · see citing works
Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation
Giuliani, N., Ferretti, M., Bolzoni, M., Storti, P., Lazzaretti, M., Palma, B. D., Bonomini, S., Martella, E., Agnelli, L., Neri, A., et al. (2012) · Leukemia · doi:10.1038/leu.2011.381 · Cited by 140 · see citing works
The Role of the Osteocyte in Bone and Nonbone Disease
Bonewald, L. F. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.09.003 · Cited by 130 · see citing works
Intercellular Cross-Talk Among Bone Cells: New Factors and Pathways
Sims, N. A., & Walsh, N. C. (2012) · Current Osteoporosis Reports · doi:10.1007/s11914-012-0096-1 · Cited by 126 · see citing works
The RANK–RANKL–OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer
León-Oliva, D. D., Barrena-Blázquez, S., Jiménez-Álvarez, L., Fraile‐Μartinez, O., Montero, C. G., López-González, L., Torres‐Carranza, D., García-Puente, L. M., Carranza, S. T., Álvarez-Mon, M. Á., et al. (2023) · Medicina · doi:10.3390/medicina59101752 · Cited by 136 · see citing works
The roles of osteocytes in alveolar bone destruction in periodontitis
Huang, X., Xie, M.-R., Xie, Y.-L., Mei, F., Lu, X., Li, X.-S., & Chen, L.-L. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02664-7 · Cited by 110 · see citing works
Functions of the osteocyte network in the regulation of bone mass
Komori, T. (2013) · Cell and Tissue Research · doi:10.1007/s00441-012-1546-x · Cited by 110 · see citing works
Álvarez, C., Monasterio, G., Cavalla, F., Córdova, L. A., Hernández, M., Heymann, D., Garlet, G. P., Sorsa, T. A., Pärnänen, P., Lee, H., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01664 · Cited by 111 · see citing works
HIF‐1α facilitates osteocyte‐mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro
Zhu, J., Tang, Y., Wu, Q., Ji, Y., Feng, Z., & Kang, F. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28721 · Cited by 108 · see citing works
Fontani, F., Marcucci, G., Iantomasi, T., Brandi, M. L., & VINCENZINI, M. T. (2015) · Calcified Tissue International · doi:10.1007/s00223-015-9961-0 · Cited by 89 · see citing works
Middleton, K., Al‐Dujaili, S. A., Mei, X., Günther, A., & You, L. (2017) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2017.05.012 · Cited by 85 · see citing works
Self-citationOsteocyte apoptosis is mechanically regulated and induces angiogenesis in vitro
Cheung, W., Liu, C., Tonelli-Zasarsky, R. L. M., Simmons, C. A., & You, L. (2010) · Journal of Orthopaedic Research® · doi:10.1002/jor.21283 · Cited by 83 · see citing works
Self-citationRen, L., Song, Z., Cai, Q., Chen, R.-X., Zou, Y., Fu, Q., & Ma, Y. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.109 · Cited by 72 · see citing works
Moonlighting osteoclasts as undertakers of apoptotic cells
Steffen, U., Keppeler, H., Ipseiz, N., Derer, A., Poller, K., Aigner, M., Schett, G. A., i, M. H., & Lauber, K. (2012) · Autoimmunity · doi:10.3109/08916934.2012.719950 · Cited by 68 · see citing works
Taddei, S. R. D. A., Queiroz‐Junior, C. M., Moura, A. P., Andrade, I., Garlet, G. P., Proudfoot, A. E. I., Teixeira, M. M., & Silva, T. A. (2012) · Bone · doi:10.1016/j.bone.2012.09.036 · Cited by 67 · see citing works
Role of osteocytes in multiple myeloma bone disease
Delgado‐Calle, J., Bellido, T., & Roodman, G. D. (2014) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000090 · Cited by 63 · see citing works
Osteocytes: central conductors of bone biology in normal and pathological conditions
Neve, A., Corrado, A., & Cantatore, F. P. (2011) · Acta Physiologica · doi:10.1111/j.1748-1716.2011.02385.x · Cited by 62 · see citing works
Sadek, K. M., Moshy, S. E., Radwan, I. A., Rady, D., Abbass, M. M. S., El‐Rashidy, A. A., Dörfer, C. E., & El‐Sayed, K. M. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054599 · Cited by 62 · see citing works
Wu, D., Schaffler, M. B., Weinbaum, S., & Spray, D. C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310003110 · Cited by 56 · see citing works
Hoefert, S., Yuan, A., Munz, A., Grimm, M. R., ElAyouti, A., & Reinert, S. (2017) · Journal of Cranio-Maxillofacial Surgery · doi:10.1016/j.jcms.2017.01.013 · Cited by 56 · see citing works
Choy, M. H. V., Wong, R. M. Y., Chow, S. K., Li, M. C. M., Chim, Y. N., Li, T. K., Ho, W. T., Cheng, J. C. Y., & Cheung, W. (2019) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2019.07.005 · Cited by 56 · see citing works
Osteoimmunology in Periodontitis: Local Proteins and Compounds to Alleviate Periodontitis
Sirisereephap, K., Maekawa, T., Tamura, H., Hiyoshi, T., Domon, H., Isono, T., Terao, Y., Maeda, T., & Tabeta, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105540 · Cited by 56 · see citing works
Søe, K., Delaisse, J.-M., & Borggaard, X. G. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.05.016 · Cited by 49 · see citing works
Wei, L., Chai, S., Chen, Y., Zhang, H., Li, J., & Qin, N. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01331-2 · Cited by 53 · see citing works
Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction
Kringelbach, T. M., Aslan, D., Novak, I., Ellegaard, M., Syberg, S., Andersen, C. K. B., Kristiansen, K. A., Vang, O., Schwarz, P., & Jørgensen, N. R. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.08.016 · Cited by 49 · see citing works
Wu, X., Feng, X., He, Y., Gao, Y., Yang, S., Shao, Z., Yang, C., Wang, H., & Ye, Z. (2016) · Osteoporosis International · doi:10.1007/s00198-015-3474-6 · Cited by 46 · see citing works
The role of the sphingosine-1-phosphate signaling pathway in osteocyte mechanotransduction
Zhang, J., Zhao, Y., Liu, C., Han, E. S., Xue, Y., Lidington, D., Bolz, S., & You, L. (2015) · Bone · doi:10.1016/j.bone.2015.05.017 · Cited by 40 · see citing works
Self-citationZhang, Y., Yan, M., YU, A.-Y., Mao, H., & Zhang, J. (2012) · Toxicology · doi:10.1016/j.tox.2012.04.002 · Cited by 40 · see citing works
Yoshitaka, T., Ishida, S., Mukai, T., Kittaka, M., Reichenberger, E., & Ueki, Y. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2125 · Cited by 38 · see citing works
Is Diabetic Skeletal Fragility Associated with Microvascular Complications in Bone?
Fajardo, R. J. (2017) · Current Osteoporosis Reports · doi:10.1007/s11914-017-0341-8 · Cited by 37 · see citing works
Duan, L., Zuo, J., Zhang, F., Li, B., Xu, Z., Zhang, H., Yang, B., Song, W., & Jiang, J. (2020) · International Journal of Nanomedicine · doi:10.2147/ijn.s244453 · Cited by 35 · see citing works
Webster, J. M., Fenton, C. G., LANGEN, R. C. J., & Hardy, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225768 · Cited by 34 · see citing works
Role of nitric oxide in orthodontic tooth movement (Review)
Yan, T., Xie, Y., He, H., Fan, W., & Huang, F. P. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.5001 · Cited by 34 · see citing works
Domazetovic, V., Marcucci, G., Pierucci, F., Bruno, G., Mannelli, L. D. C., Ghelardini, C., Brandi, M. L., Iantomasi, T., Meacci, E., & VINCENZINI, M. T. (2019) · FEBS Open Bio · doi:10.1002/2211-5463.12634 · Cited by 33 · see citing works
The role of osteocytes during experimental orthodontic tooth movement: A review
Murshid, S. A. (2016) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2016.09.001 · Cited by 33 · see citing works
Bone Response of Loaded Periodontal Ligament
Dutra, E. H., Nanda, R., & Yadav, S. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0328-x · Cited by 32 · see citing works
From 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 26 · see citing works
Unfractionated Heparin Promotes Osteoclast Formation in Vitro by Inhibiting Osteoprotegerin Activity
Li, B., Lü, D., Chen, Y., Zhao, M., & Zuo, L. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17040613 · Cited by 27 · see citing works
Ay, B., Parolia, K., Liddell, R. S., Qiu, Y., Grasselli, G., Cooper, D. M. L., & Davies, J. E. (2020) · Communications Biology · doi:10.1038/s42003-019-0747-1 · Cited by 27 · see citing works
Assembling the Puzzle Pieces. Insights for in Vitro Bone Remodeling
Krasnova, O. A., & Neganova, I. E. (2023) · Stem Cell Reviews and Reports · doi:10.1007/s12015-023-10558-6 · Cited by 26 · see citing works
Barbe, M. F., Massicotte, V. S., Assari, S., Monroy, M. A., Frara, N. A., Harris, M. Y., Amin, M., King, T. E., Cruz, G. E., & Popoff, S. N. (2018) · Bone · doi:10.1016/j.bone.2018.02.014 · Cited by 26 · see citing works
The Effect of OSM on MC3T3-E1 Osteoblastic Cells in Simulated Microgravity with Radiation
Goyden, J., Tawara, K., Hedeen, D. S., Willey, J. S., Oxford, J. T., & Jorcyk, C. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127230 · Cited by 25 · see citing works
Migration and differentiation of osteoclast precursors under gradient fluid shear stress
Gao, Y., Li, T., Sun, Q., Ye, C., Guo, M., Chen, Z., Chen, J., & Huo, B. (2019) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-019-01171-z · Cited by 25 · see citing works
Tang, A., Shu, Q., Jia, S., Lai, Z., & Tian, J. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s486622 · Cited by 24 · see citing works
Biswas, L., Niveria, K., & Verma, A. K. (2022) · Exploration of Medicine · doi:10.37349/emed.2022.00102 · Cited by 24 · see citing works
Mind Gaps and Bone Snaps: Exploring the Connection Between Alzheimer’s Disease and Osteoporosis
Wang, H. S., Karnik, S. J., Margetts, T. J., Plotkin, L. I., Movilă, A., Fehrenbacher, J. C., Kacena, M. A., & Oblak, A. L. (2024) · Current Osteoporosis Reports · doi:10.1007/s11914-023-00851-1 · Cited by 23 · see citing works
Zhao, R., Chen, N.-N., Zhou, X., Miao, P., Hu, C., Liu, Q., Yu, Q., Zhang, J., Nie, H., Chen, X., et al. (2014) · Journal of Translational Medicine · doi:10.1186/s12967-014-0330-y · Cited by 22 · see citing works
Domazetovic, V., Fontani, F., Marcucci, G., Iantomasi, T., Brandi, M. L., & VINCENZINI, M. T. (2017) · FEBS Open Bio · doi:10.1002/2211-5463.12216 · Cited by 22 · see citing works
Bratengeier, C., Bakker, A. D., & Fahlgren, A. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27976 · Cited by 21 · see citing works
Jiang, A., Xu, P., Sun, S., Zhao, Z., Tan, Q., Li, W., Song, C., & Leng, H. (2021) · Connective Tissue Research · doi:10.1080/03008207.2020.1870969 · Cited by 21 · see citing works
Molecular Interactions between Dietary Lipids and Bone Tissue during Aging
Romero‐Márquez, J. M., Varela‐López, A., Navarro‐Hortal, M. D., Badillo-Carrasco, A., Forbes-Hernández, T. Y., Giampieri, F., Azpíroz, I. D., Madrigal, L., Battino, M. A., & Quiles, J. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126473 · Cited by 20 · see citing works
Mulcahy, L., Curtin, C. M., McCoy, R., O’Brien, F. J., Taylor, D. M., Lee, T., & Duffy, G. P. (2015) · European Cells and Materials · doi:10.22203/ecm.v030a19 · Cited by 19 · see citing works
Osteocyte Alterations Induce Osteoclastogenesis in an In Vitro Model of Gaucher Disease
Bondar, C., Ormazábal, M., Crivaro, A., Ferreyra-Compagnucci, M., Delpino, M. V., Rozenfeld, P. A., & Mucci, J. M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010112 · Cited by 17 · see citing works
Flow-Induced Migration of Osteoclasts and Regulations of Calcium Signaling Pathways
Liu, C., Li, S., Ji, B., & Huo, B. (2014) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-014-0372-5 · Cited by 13 · see citing works
Liu, C., Zhang, X., Wu, M. Y., & You, L. (2015) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2015.10.018 · Cited by 13 · see citing works
Self-citationThe Osteocyte as an Orchestrator of Bone Remodeling: An Engineer’s Perspective
van Oers, R. F. M., Klein‐Nulend, J., & Bacabac, R. G. (2014) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-014-9154-9 · Cited by 12 · see citing works
Modeling TGF-β in Early Stages of Cancer Tissue Dynamics
Ascolani, G., & Lió, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088533 · Cited by 11 · see citing works
Kottmann, V., Nienhaus, M., Drees, P., Gercek, E., & Ritz, U. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189551 · Cited by 12 · see citing works
Involvement of Osteocytes in the Action of Pasteurella multocida Toxin
Heni, H., Ebner, J. K., Schmidt, G., Aktories, K., & Orth, J. H. C. (2018) · Toxins · doi:10.3390/toxins10080328 · Cited by 10 · see citing works
How rare bone diseases have informed our knowledge of complex diseases
Johnson, M. L. (2016) · BoneKEy Reports · doi:10.1038/bonekey.2016.69 · Cited by 9 · see citing works
Tang, Q., Su, Y., Fan, C., Chung, R., Hassanshahi, M., Peymanfar, Y., & Xian, C. J. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3597 · Cited by 9 · see citing works
RetractedCoupling: The Influences of Immune and Bone Cells
Sims, N. A., Martin, T. J., & Quinn, J. M. W. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800571-2.00010-4 · Cited by 9 · see citing works
Cao, Z., Xu, R., Zheng, W., Ma, L., He, Y., Chen, T., & Liu, H. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202500523 · Cited by 8 · see citing works
Effects of oestrogen deficiency on bone mineralisation in girls during "adolescent crisis".
Sowińska-Przepiera, E., Andrysiak-Mamos, E., Jarząbek‐Bielecka, G., Friebe, Z., & Syrenicz, A. (2011) · PubMed · Cited by 7 · see citing works
Osteocytes communicate with osteoclast lineage cells via RANKL
Matsuo, K. (2012) · IBMS BoneKEy · doi:10.1038/bonekey.2012.36 · Cited by 7 · see citing works
Natural hydrogels for bone tissue engineering
Parmentier, L., & Vlierberghe, S. V. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820508-2.00009-x · Cited by 7 · see citing works
Sinclair, C., Birch, H. L., Smith, R. K. W., & Goodship, A. E. (2013) · Elsevier eBooks · doi:10.1016/b978-0-7020-4771-8.00008-9 · Cited by 6 · see citing works
Kahla, R. B., & Barkaoui, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-88467-9.00002-3 · Cited by 5 · see citing works
Risk of ozone exposure-induced fracture
Lu, S., Xu, R., Gong, M., Zha, Y., Li, N., Chen, J., Liu, X., & Jiang, X. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1153256 · Cited by 5 · see citing works
Effect of Enterococcus faecalis on osteoclastogenesis under cobalt-mimicked hypoxia in vitro
Zhou, F., Li, X., Chang, X., Geng, Z., Hao, W., Deng, J., Wong, H. M., & Wang, S. (2022) · Microbial Pathogenesis · doi:10.1016/j.micpath.2022.105964 · Cited by 3 · see citing works
The role of oxidative stress and antioxidants in older individuals with osteoporotic hip fractures
Aydın, M. (2025) · Turkish Journal of Trauma and Emergency Surgery · doi:10.14744/tjtes.2024.89335 · Cited by 3 · see citing works
The role of coenzyme Q10 in the protection of bone health during aging
Quiles, J. L., Romero‐Márquez, J. M., Navarro‐Hortal, M. D., Battino, M. A., & Varela‐López, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818698-5.00017-1 · Cited by 3 · see citing works
Panahipour, L., Abbasabadi, A. O., Kaiser, V., Sordi, M. B., Kargarpour, Z., & Gruber, R. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144061 · Cited by 2 · see citing works
RETRACTED ARTICLE: Titanium particles damage osteocytes and inhibit osteoblast differentiation
Chen, L., Wang, Z., Xu, W., & Dong, Q. (2020) · Journal of Experimental Orthopaedics · doi:10.1186/s40634-020-00268-0 · Cited by 2 · see citing works
RetractedBone Cells: Osteoblast/Osteoclast/Osteocyte
Rucci, N., & Teti, A. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64347-7 · Cited by 2 · see citing works
Structure and Function of the Musculoskeletal System
Gallagher, S., & Barbe, M. F. (2022) · doi:10.1002/9781119640172.ch3 · Cited by 2 · see citing works
Rady, D., Moshy, S. E., Abbass, M. M. S., Sadek, K. M., El‐Rashidy, A. A., Radwan, I. A., & El‐Sayed, K. M. F. (2023) · Springer eBooks · doi:10.1007/978-981-99-0846-2_51-1 · Cited by 1 · see citing works
Osteocytes and Bone Regeneration
Atkins, G. J., Prideaux, M., & Findlay, D. M. (2014) · Mechanical engineering series · doi:10.1007/978-3-319-13266-2_3 · Cited by 1 · see citing works
Origin and Differentiation of Osteoclasts
Sanjay, A., & Charles, J. F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11161-4 · Cited by 1 · see citing works
Osteocytes, bone remodeling and parathyroid hormone
Datta, N. S. (2012) · Endocrinology Studies · doi:10.4081/es.2012.e8
Bone Formation and Skeletal Aging - The effects of oxygen tension and DNA repair
Nicolaije, C. (2012) · RePub (Erasmus University Rotterdam)
Liu, C. (2016) · TSpace (University of Toronto)
The Role of Osteocyte Apoptosis on Osteoclast Precursor Recruitment
Cheung, W.-Y. (2013) · TSpace (University of Toronto)
Osteoblast Oncostatin M Signaling in Modeled Spaceflight
Goyden, J. (2014) · ScholarWorks (Boise State University)
- Authors
- Al‐Dujaili, S. A., Lau, E., Al‐Dujaili, H., Tsang, K., Guenther, A., & You, L.
- Affiliations
- University of Toronto (CA)
- Western University (CA)
- Corresponding author
- You, Lidan
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2011-08-18
- Volume
- 112
- Issue
- 9
- Pages
- 2412-2423
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W2038645339
- Cited by
- 118
- References
- 47
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 10 · 2013: 7 · 2012: 12
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Missouri
- University of Toronto
- Natural Sciences and Engineering Research Council of Canada (341704)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- osteocyte apoptosis, osteoclastogenesis, bone resorption, microdamage, RANKL, macrophage colony-stimulating factor, vascular endothelial growth factor, osteoprotegerin, soluble factors, MLO-Y4 cells, RAW 264.7 macrophages, fatigue loading
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Cell Movement, Monocytes, Osteoclasts, Osteocytes, Up-Regulation, Gene Expression, Macrophage Colony-Stimulating Factor, Culture Media, Serum-Free, Culture Media, Conditioned, Apoptosis, Vascular Endothelial Growth Factor A, Cell Size, Mice, Osteoprotegerin, RANK Ligand
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