No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice
Open accessAbstract
Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDRΔ/Δ) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD). Thereafter, VDRΔ/Δ mice received either the CD, a normal diet (ND), or the RD. At baseline, BMDD and OLS characteristics were similar in VDRΔ/Δ and wild-type mice. The CD induced large cortical pores, osteomalacia, and a reduced epiphyseal average degree of mineralization in the VDRΔ/Δ mice relative to the baseline (−9.5%, p < 0.05 after two months and −10.3%, p < 0.01 after five months of the CD). Switching VDRΔ/Δ mice on the CD back to the RD fully restored BMDD to baseline values. However, OLS remained unchanged in all groups of mice, independent of diet. We conclude that adult VDRΔ/Δ animals on an RD lack any skeletal abnormalities, suggesting that VDR signaling is dispensable for normal bone mineralization as long as mineral homeostasis is normal. Our findings also indicate that VDRΔ/Δ mice attempt to correct a calcium challenge by enhanced osteoclastic resorption rather than by osteocytic osteolysis.
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The efficiency of this additional and independent component of bone remodeling in calcium homeostasis under PTH regulation remains unclear because of the lack of a relationship between serum PTH and osteocyte lacuna characteristics.
“The efficiency of this additional and independent component of bone remodeling in calcium homeostasis under PTH regulation remains unclear because of the lack of a relationship between serum PTH and osteocyte lacuna characteristics.87”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [87]
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Cites
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638 · see citing works
Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice
Bouillon, R., Carmeliet, G., Verlinden, L., van Etten, E., Verstuyf, A., Luderer, H. F., Lieben, L., Mathieu, C., & Demay, M. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0004 · Cited by 1,783 · see citing works
Yoshizawa, T., Handa, Y., Uematsu, Y., Takeda, S., Sekine, K., Yoshihara, Y., Kawakami, T., Arioka, K., Sato, H., Uchiyama, Y., et al. (1997) · Nature Genetics · doi:10.1038/ng0897-391 · Cited by 1,175 · see citing works
Li, Y. C., Pirro, A. E., Amling, M., Delling, G., Baron, R., Bronson, R. T., & Demay, M. B. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9831 · Cited by 955 · see citing works
Bone mineralization density distribution in health and disease
Roschger, P., Paschalis, E. P., Fratzl, P., & Klaushofer, K. (2007) · Bone · doi:10.1016/j.bone.2007.10.021 · Cited by 650 · see citing works
Self-citationAge-Related Changes in Trabecular Architecture Differ in Female and Male C57BL/6J Mice
Glatt, V., CANALIS, E. M., Stadmeyer, L., & Bouxsein, M. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070507 · Cited by 609 · see citing works
Li, Y. C., Amling, M., Pirro, A. E., et al. (1998) · Endocrinology · doi:10.1210/endo.139.10.6262 · Cited by 524 · see citing works
Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation
Qing, H., Ardeshirpour, L., Divieti Pajevic, P., Dusevich, V., Jähn, K., Kato, S., Wysolmerski, J., & Bonewald, L. F. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1567 · Cited by 489 · see citing works
Roschger, P., Fratzl, P., Eschberger, J., et al. (1998) · Bone · doi:10.1016/s8756-3282(98)00112-4 · Cited by 457 · see citing works
Self-citationLieben, L., Masuyama, R., Torrekens, S., Looveren, R. V., Schrooten, J., Baatsen, P., Lafage‐Proust, M., Dresselaers, T., Feng, J. Q., Bonewald, L. F., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci45890 · Cited by 366 · see citing works
The role of vitamin D in the endocrinology controlling calcium homeostasis
Fleet, J. C. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.04.008 · Cited by 298 · see citing works
Erben, R. G., Soegiarto, D. W., Weber, K., Zeitz, U., Lieberherr, M., Gniadecki, R., Möller, G., Adamski, J., & Balling, R. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.7.0866 · Cited by 291 · see citing works
Self-citationOsteocytic osteolysis observed in rats to which parathyroid hormone was continuously administered
Tazawa, K., Hoshi, K., Kawamoto, S., Tanaka, M., Ejiri, S., & Ozawa, H. (2004) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-004-0519-x · Cited by 124 · see citing works
Physiological and pathological osteocytic osteolysis.
Tsourdi, E. A., Jähn, K., Rauner, M., Busse, B., & Bonewald, L. F. (2018) · Europe PMC (PubMed Central) · Cited by 115 · see citing works
Osteocyte-directed bone demineralization along canaliculi
Nango, N., Kubota, S., Hasegawa, T., Yashiro, W., Momose, A., & Matsuo, K. (2015) · Bone · doi:10.1016/j.bone.2015.12.006 · Cited by 93 · see citing works
Roschger, P., Dempster, D. W., Zhou, H., et al. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070120 · Cited by 79 · see citing works
Self-citationVitamin D regulates osteocyte survival and perilacunar remodeling in human and murine bone
Rolvien, T., Krause, M., Jeschke, A., Yorgan, T., Püschel, K., Schinke, T., Busse, B., Demay, M. B., & Amling, M. (2017) · Bone · doi:10.1016/j.bone.2017.06.022 · Cited by 74 · see citing works
Osteocytic osteolysis: time for a second look?
Wysolmerski, J. J. (2012) · BoneKEy Reports · doi:10.1038/bonekey.2012.229 · Cited by 72 · see citing works
Blouin, S., Fratzl-Zelman, N., Glorieux, F. H., Roschger, P., Klaushofer, K., Marini, J. C., & Rauch, F. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3180 · Cited by 69 · see citing works
Self-citationHeveran, C. M., Rauff, A., King, K. B., Carpenter, R. D., & Ferguson, V. L. (2018) · Bone · doi:10.1016/j.bone.2018.01.018 · Cited by 57 · see citing works
Streicher, C., Zeitz, U., Andrukhova, O., Rupprecht, A., Pohl, E. E., Larsson, T. E., Windisch, W. M., Lanske, B., & Erben, R. G. (2012) · Endocrinology · doi:10.1210/en.2011-1878 · Cited by 56 · see citing works
Self-citationLieben, L., & Carmeliet, G. (2012) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2012.09.019 · Cited by 39 · see citing works
Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH)
Fratzl‐Zelman, N., Gamsjaeger, S., Blouin, S., et al. (2020) · Journal of Structural Biology · doi:10.1016/j.jsb.2020.107556 · Cited by 37 · see citing works
Self-citationVitamin D endocrine system and osteocytes
Lanske, B., Densmore, M., & Erben, R. G. (2014) · BoneKEy Reports · doi:10.1038/bonekey.2013.228 · Cited by 36 · see citing works
Self-citationNormal mineralization and nanostructure of sclerotic bone in mice overexpressing Fra-1
Roschger, P., Matsuo, K., Misof, B. M., et al. (2004) · Bone · doi:10.1016/j.bone.2004.01.004 · Cited by 32 · see citing works
Self-citationAdynamic Bone Decreases Bone Toughness During Aging by Affecting Mineral and Matrix
Ng, A., Omelon, S. J., Variola, F., Allo, B. A., Willett, T. L., Alman, B. A., & Grynpas, M. D. (2015) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2702 · Cited by 31 · see citing works
Nawrot-Wawrzyniak, K., Misof, B. M., Roschger, P., et al. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2012.12.010 · Cited by 31 · see citing works
Self-citationChristakos, S., Li, S., Cruz, J. D. L., Verlinden, L., & Carmeliet, G. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_338 · Cited by 28 · see citing works
Misof, B. M., Blouin, S., Roschger, P., Werzowa, J. M., Klaus Klaushofer, A., & Lehmann, G. (2019) · PubMed Central · Cited by 25 · see citing works
Self-citationSex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice
Ryan, J. W., Starczak, Y., Tsangari, H., Sawyer, R. K., Davey, R. A., Atkins, G. J., Morris, H. A., & Anderson, P. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.12.005 · Cited by 16 · see citing works
Weber, K., Zeitz, U., Bergow, C., et al. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0080904 · Cited by 12 · see citing works
Biomechanical and Bone Material Properties of Schnurri‐3 Null Mice
Hofstaetter, J. G., Misof, B. M., Jones, D. C., et al. (2019) · JBMR Plus · doi:10.1002/jbm4.10226 · Cited by 5 · see citing works
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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
- Authors
- Misof, B. M., Blouin, S., Hofstaetter, J. G., Roschger, P., Zwerina, J., & Erben, R. G.
- Affiliations
- Hanusch Hospital (AT)
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Misof, Barbara M.
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-10-27
- Volume
- 21
- Issue
- 21
- Pages
- 7989
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7662929
- OpenAlex
- W3097786706
- Cited by
- 9
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 4
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Allgemeine Unfallversicherungsanstalt
- 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
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Keywords
- secondary hyperparathyroidism, osteocyte lacunae, low calcium diet, osteomalacia, osteoclast resorption, mineral homeostasis
- MeSH terms
- Animals, Calcium, Dietary, Disease Models, Animal, Homeostasis, Hyperparathyroidism, Secondary, Male, Osteocytes, Osteolysis, Phenotype, Signal Transduction, Bone Density, Receptors, Calcitriol, Mice
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