Osteocyte Apoptosis and Absence of Bone Remodeling in Human Auditory Ossicles and Scleral Ossicles of Lower Vertebrates: A Mere Coincidence or Linked Processes?
Open accessAbstract
Considering the pivotal role as bone mechanosensors ascribed to osteocytes in bone adaptation to mechanical strains, the present study analyzed whether a correlation exists between osteocyte apoptosis and bone remodeling in peculiar bones, such as human auditory ossicles and scleral ossicles of lower vertebrates, which have been shown to undergo substantial osteocyte death and trivial or no bone turnover after cessation of growth. The investigation was performed with a morphological approach under LM (by means of an in situ end-labeling technique) and TEM. The results show that a large amount of osteocyte apoptosis takes place in both auditory and scleral ossicles after they reach their final size. Additionally, no morphological signs of bone remodeling were observed. These facts suggest that (1) bone remodeling is not necessarily triggered by osteocyte death, at least in these ossicles, and (2) bone remodeling does not need to mechanically adapt auditory and scleral ossicles since they appear to be continuously submitted to stereotyped stresses and strains; on the contrary, during the resorption phase, bone remodeling might severely impair the mechanical resistance of extremely small bony segments. Thus, osteocyte apoptosis could represent a programmed process devoted to make stable, when needed, bone structure and mechanical resistance.
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Bone marrow stroma is present in all bones except auditory ossicles.
“Anatomically, the BM stroma is part of the skeleton and is present in all bones except auditory ossicles, which therefore do not undergo remodeling.274”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [274]
Cites
Programmed Cell Death in Animal Development
Jacobson, M. D., Weil, M., & RAFF, M. C. (1997) · Cell · doi:10.1016/s0092-8674(00)81873-5 · Cited by 2,685 · see citing works
Bone “mass” and the “mechanostat”: A proposal
Frost, H. M. (1987) · The Anatomical Record · doi:10.1002/ar.1092190104 · Cited by 2,132 · see citing works
Romer, A. S. (1957) · AIBS Bulletin · doi:10.2307/1292217 · Cited by 1,210 · see citing works
Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
Hughes, D. E., Wright, K. R., Uy, H. L., Sasaki, A., Yoneda, T., Roodman, D., Mundy, G. R., & Boyce, B. F. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650101008 · Cited by 1,039 · see citing works
Fedde, M. R. (1989) · Poultry Science · doi:10.3382/ps.0681599 · Cited by 848 · see citing works
Osteoblast Programmed Cell Death (Apoptosis): Modulation by Growth Factors and Cytokines
Jilka, R. L., Weinstein, R. S., Bellido, T., Parfitt, A. M., & Manolagas, S. C. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.5.793 · Cited by 578 · see citing works
Origins of avian ocular and periocular tissues
Johnston, M. C., Noden, D. M., Hazelton, R. D., Coulombre, J. L., & Coulombre, A. J. (1979) · Experimental Eye Research · doi:10.1016/0014-4835(79)90164-7 · Cited by 493 · see citing works
The control of avian cephalic neural crest cytodifferentiation
Noden, D. M. (1978) · Developmental Biology · doi:10.1016/0012-1606(78)90201-4 · Cited by 425 · see citing works
Birds—Their structure and function
Curtis, P. E. (1985) · British Veterinary Journal · doi:10.1016/0007-1935(85)90051-x · Cited by 393 · see citing works
King, A. S., & McLelland, J. (1981) · Medical Entomology and Zoology · Cited by 334 · see citing works
Naturally occurring cell death during neural development
Oppenheim, R. W. (1985) · Trends in Neurosciences · doi:10.1016/0166-2236(85)90175-4 · Cited by 309 · see citing works
Nineteenth century research on naturally occurring cell death and related phenomena
Clarke, P. H., & Clarke, S. (1996) · Anatomy and Embryology · doi:10.1007/bf00214700 · Cited by 268 · see citing works
Morphological study of intercellular junctions during osteocyte differentiation
Palumbo, C., Palazzini, S., & Marotti, G. (1990) · Bone · doi:10.1016/8756-3282(90)90134-k · Cited by 252 · see citing works
Self-citationIdentification of apoptotic changes in osteocytes in normal and pathological human bone
Noble, B. S., Stevens, H., Loveridge, N., & Reeve, J. (1997) · Bone · doi:10.1016/s8756-3282(96)00365-1 · Cited by 230 · see citing works
Kogianni, G., Mann, V., & Noble, B. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080207 · Cited by 221 · see citing works
Birds: Their Structure and Function
King, A. S., & McLelland, J. (1983) · Cited by 214 · see citing works
Osteocyte function, osteocyte death and bone fracture resistance
Noble, B., & REEVE, J. (2000) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(99)00174-4 · Cited by 211 · see citing works
Frost, H. M. (1960) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-196042010-00011 · Cited by 193 · see citing works
The structure of bone tissues and the cellular control of their deposition.
Marotti, G. (1997) · PubMed · Cited by 185 · see citing works
Palumbo, C., Palazzini, S., Zaffe, D., & Marotti, G. (1990) · Cells Tissues Organs · doi:10.1159/000146907 · Cited by 151 · see citing works
Self-citationBronckers, A. L. J. J., Goei, W., Luo, G., Karsenty, G., D’Souza, R. N., Lyaruu, D. M., & Burger, E. H. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110913 · Cited by 145 · see citing works
The Phylogenetic Definition of Reptilia
MODESTO, S. P., & Anderson, J. S. (2004) · Systematic Biology · doi:10.1080/10635150490503026 · Cited by 122 · see citing works
Apoptosis in bone physiology and disease.
Hughes, D. E., & Boyce, B. F. (1997) · Molecular Pathology · doi:10.1136/mp.50.3.132 · Cited by 108 · see citing works
Apoptosis: Programmed cell death in fetal development
Haanen, C., & Vermes, I. (1996) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/0301-2115(95)02261-9 · Cited by 97 · see citing works
Apoptosis: molecular mechanisms and implications for human disease
Orrenius, S. (1995) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1995.tb00881.x · Cited by 95 · see citing works
The osteocyte as a wiring transmission system.
Marotti, G. (2000) · PubMed · Cited by 81 · see citing works
Weaver, V. M., & Bissell, M. J. (1999) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1018781325716 · Cited by 77 · see citing works
Functional determinants of bone structure: Beyond Wolff's law of bone transformation
Turner, C. H. (1992) · Bone · doi:10.1016/8756-3282(92)90082-8 · Cited by 77 · see citing works
Skeletal elements in the vertebrate eye and adnexa: Morphological and developmental perspectives
Franz‐Odendaal, T. A., & Vickaryous, M. K. (2006) · Developmental Dynamics · doi:10.1002/dvdy.20718 · Cited by 76 · see citing works
Apoptosis in Nontumorous and Neoplastic Human Pituitaries
Kulig, E., Jin, L. G., Qian, X., Horváth, É., Kovács, K., Ştefăneanu, L., Scheithauer, B. W., & Lloyd, R. V. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65323-0 · Cited by 68 · see citing works
Skeletal elements within teleost eyes and a discussion of their homology
Franz‐Odendaal, T. A., & Hall, B. K. (2006) · Journal of Morphology · doi:10.1002/jmor.10479 · Cited by 61 · see citing works
Morphometric investigation on osteocytes in human auditory ossicles
Marotti, G., Farneti, D., Remaggi, F., & Tartari, F. (1998) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/s0940-9602(98)80106-4 · Cited by 58 · see citing works
Toward understanding the development of scleral ossicles in the chicken, Gallus gallus
Franz‐Odendaal, T. A. (2008) · Developmental Dynamics · doi:10.1002/dvdy.21754 · Cited by 52 · see citing works
Regulation of programmed cell death or apoptosis in atherosclerosis.
Geng, Y. (1997) · PubMed · Cited by 43 · see citing works
Detection of soluble Fas mRNA using in situ reverse transcription-polymerase chain reaction.
Lee, S. H., Kim, S. Y., Lee, J. Y., Shin, M. S., Dong, S. M., Na, E. Y., Park, W. S., Kim, K. M., Kim, C. S., Kim, S. H., et al. (1998) · PubMed · Cited by 40 · see citing works
Establishment of the scleral cartilage in the chick
Stewart, P. A., & McCallion, D. J. (1975) · Developmental Biology · doi:10.1016/0012-1606(75)90114-1 · Cited by 33 · see citing works
Coulombre, A. J., & Coulombre, J. L. (1973) · Developmental Biology · doi:10.1016/0012-1606(73)90136-x · Cited by 32 · see citing works
Palumbo, C., Ferretti, M., Ardizzoni, A., Zaffe, D., & Marotti, G. (2001) · PubMed · Cited by 31 · see citing works
Self-citationOsteocyte-Bone Lining Cell System at the Origin of Steady Ionic Current in Damaged Amphibian Bone
Rubinacci, A., Villa, I., Benelli, F. D., Borgo, E., Ferretti, M., Palumbo, C., & Marotti, G. (1998) · Calcified Tissue International · doi:10.1007/s002239900536 · Cited by 30 · see citing works
Self-citationFyfe, D. M., & Hall, B. K. (1983) · Development · doi:10.1242/dev.73.1.69 · Cited by 28 · see citing works
Tanimoto, T., Tanaka, S., Haruma, K., Yoshihara, M., Sumii, K., Kajiyama, G., & Shimamoto, F. (1998) · Diseases of the Colon & Rectum · doi:10.1007/bf02237053 · Cited by 23 · see citing works
FRACTURED SCLERAL OSSICLES IN A RED TAIL HAWK
Lindley, D. M., Hathcock, J. T., Miller, W. W., & DiPinto, M. N. (1988) · Veterinary Radiology · doi:10.1111/j.1740-8261.1988.tb01501.x · Cited by 18 · see citing works
Warheit, K. I., Good, D. A., & de Queiroz, K. (1989) · Smithsonian Digital Repository (Smithsonian Institution) · Cited by 14 · see citing works
Quantitative Evaluation of Postnatal Bone Growth in the Auditory Ossicles of the Dog
Roberto, M. (1978) · Annals of Otology Rhinology & Laryngology · doi:10.1177/000348947808700315 · Cited by 10 · see citing works
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The Role of Osteocytes in Age-Related Bone Loss
Jilka, R. L., & O’Brien, C. A. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0297-0 · Cited by 136 · see citing works
Rolvien, T., Schmidt, F. N., Milovanovic, P. D., Jähn, K., Riedel, C., Butscheidt, S., Püschel, K., Jeschke, A., Amling, M., & Busse, B. (2018) · Scientific Reports · doi:10.1038/s41598-018-19803-2 · Cited by 61 · see citing works
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- Authors
- Palumbo, C., Cavani, F., Sena, P., Benincasa, M., & Ferretti, M.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Palumbo, Carla
- Venue
- Calcified Tissue International
- Published
- 2012-01-31
- Volume
- 90
- Issue
- 3
- Pages
- 211-218
- ISSN
- 0171-967X (ISSN-L)
- 1432-0827
- OpenAlex
- W2013257666
- Cited by
- 22
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 4 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 1
- FWCI
- 0.39
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Calcified Tissue International (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- 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 › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Keywords
- osteocyte apoptosis, bone remodeling, ossicular chain, scleral ossicles, lower vertebrates, bone mechanosensing, bone mechanotransduction, bone resorption, mechanical adaptation, programmed cell death
- MeSH terms
- Adolescent, Adult, Aged, Animals, Animal Structures, Chick Embryo, Chickens, Ear Ossicles, Biological Evolution, Female, Humans, Lizards, Male, Middle Aged, Osteocytes, Sclera, Bone Remodeling, Apoptosis, Young Adult
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