Abstract
The otic capsule consists of dense highly mineralized compact bone. Inner ear osteoprotegerin (OPG) effectively inhibits perilabyrinthine remodeling and otic capsular bone turnover is very low compared to other bone. Consequently, degenerative changes like dead osteocytes and microcracks accumulate around the inner ear. Osteocytes are connected via canaliculi and need a certain connectivity to sustain life. Consequently, stochastic osteocyte apoptosis may disrupt the osteocytic network in unsustainable patterns leading to widespread cell death. When studying bulk-stained undecalcified human temporal bone, large clusters of dead osteocytes have been observed. Such “cellular voids” may disrupt the perilabyrinthine OPG mediated remodeling inhibition possibly leading to local remodeling. In the common ear disease otosclerosis pathological bone remodeling foci are found exclusively in the otic capsule. We believe the pathogenesis of otosclerosis is linked to the unique bony dynamics of perilabyrinthine bone and cellular voids may represent a starting point for otosclerotic remodeling. This study aims to identify and characterize cellular voids of the human otic capsule. This would allow future cellular void quantification and comparison of void and otosclerotic distribution to further elucidate the yet unknown pathogenesis of otosclerosis.





Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Andersen TL, Sondergaard TE, Skorzynska KE et al (2009) A physical mechanism for coupling bone resorption and formation in adult human bone. Am J Pathol. https://doi.org/10.2353/ajpath.2009.080627
Bloch SL, Kristensen SL, Sørensen MS (2012) The viability of perilabyrinthine osteocytes: a quantitative study using bulk-stained undecalcified human temporal bones. Anat Rec (hoboken) 295:1101–1108. https://doi.org/10.1002/ar.22492
Bloch SL, Sørensen MS (2010) The viability and spatial distribution of osteocytes in the human labyrinthine capsule: a quantitative study using vector-based stereology. Hear Res 270:65–70. https://doi.org/10.1016/j.heares.2010.09.007
Bloch SL, Sørensen MS (2016) The role of connectivity and stochastic osteocyte behavior in the distribution of perilabyrinthine bone degeneration. A Monte Carlo based simulation study. Hear Res 335:1–8. https://doi.org/10.1016/j.heares.2016.02.002
Bloch SL, Sørensen MS (2014) Unbiased stereologic estimation of the spatial distribution of Paget’s disease in the human temporal bone. Otol Neurotol 35:e1-6. https://doi.org/10.1097/MAO.0000000000000218
Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol 3(Suppl 3):131–139. https://doi.org/10.2215/CJN.04151206
Datta HK, Ng WF, Walker JA et al (2008) The cell biology of bone metabolism. J Clin Pathol 61:577–587. https://doi.org/10.1136/jcp.2007.048868
Dorph-Petersen KA, Caric D, Saghafi R et al (2009) Volume and neuron number of the lateral geniculate nucleus in schizophrenia and mood disorders. Acta Neuropathol 117:369–384. https://doi.org/10.1007/s00401-008-0410-2
Feng X, McDonald JM (2011) Disorders of Bone Remodeling. Annu Rev Pathol Mech Dis 6:121–145. https://doi.org/10.1146/annurev-pathol-011110-130203
Florencio-Silva R, Sasso GRDS, Sasso-Cerri E et al (2015) Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Biomed Res Int 2015:421746. https://doi.org/10.1155/2015/421746 (Epub 2015 J)
Frisch T, Bloch SL, Sørensen MS (2015) Prevalence, size and distribution of microdamage in the human otic capsule. Acta Otolaryngol 135:771–775. https://doi.org/10.3109/00016489.2015.1035400
Frisch T, Bretlau P, Sorensen MS (2008) Intravital microlesions in the human otic capsule. Detection, classification and pathogenetic significance revisited. ORL J Otorhinolaryngol Relat Spec 70:195–201. https://doi.org/10.1159/000124294
Frisch T, Sørensen MS, Bretlau P (2001a) Demonstration of intravital microfissures in undecalcified plastic-embedded temporal bones with the prestaining technique. Ann Otol Rhinol Laryngol 110:749–757. https://doi.org/10.1177/000348940111000810
Frisch T, Sørensen MS, Bretlau P (2001b) Recognition of basic fuchsin prestained microfissures of intravital origin with fluorescence microscopy: validation of a shortcut. Eur Arch Otorhinolaryngol 258:55–60
Frost HM (1960a) Micropetrosis. J Bone Joint Surg Am 42 A:144–150. https://doi.org/10.2106/00004623-196042010-00012
Frost HM (1960b) In vivo osteocyte death. J Bone Joint Surg Am 42-A:138–143
Gundersen HJG (1986) Stereology of arbitrary particles. J Microsc 143:3–45. https://doi.org/10.1111/j.1365-2818.1986.tb02764.x
Hansen LJ, Bloch SL, Frisch T, Sørensen MS (2020) Microcrack surface density in the human otic capsule: An unbiased stereological quantification. Anat Rec 304:961–967. https://doi.org/10.1002/ar.24535
Hanstede J, Gerrits P (1983) The effects of embedding in water-soluble plastics on the final dimensions of liver sections. J Microsc 131:79–86
Holmbeck K, Bianco P, Pidoux I et al (2005) The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone. J Cell Sci 118:147–156. https://doi.org/10.1242/jcs.01581
Howard CV, Reed MG (2010) Unbiased Stereology. QTP Publications, Colerain, Second edi
Howard V, Reid S, Baddeley A, Boyde A (1985) Unbiased estimation of particle density in the tandem scanning reflected light microscope. J Microsc 138:203–212. https://doi.org/10.1111/j.1365-2818.1985.tb02613.x
Inoue K, Mikuni-Takagaki Y, Oikawa K et al (2006) A crucial role for matrix metalloproteinase 2 in osteocytic canalicular formation and bone metabolism. J Biol Chem 281:33814–33824. https://doi.org/10.1074/jbc.M607290200
Jilka RL, Noble B, Weinstein RS (2013) Osteocyte apoptosis. Bone 54:264–271. https://doi.org/10.1016/j.bone.2012.11.038
Knothe Tate ML (2003) “Whither flows the fluid in bone?” An osteocyte’s perspective. J Biomech 36:1409–1424. https://doi.org/10.1016/S0021-9290(03)00123-4
Mendoza D, Rius M (1966) Histology of the enchondral layer of the human otic capsule: Areas of devitalized and necrotic bone. Acta Otolaryngol 62:93–100. https://doi.org/10.3109/00016486609119554
Nielsen KK, Andersen CB, Kromann-Andersen B (1995) A Comparison Between the Effects of Paraffin and Plastic Embedding of the Normal and Obstructed Minipig Detrusor Muscle Using the Optical Dissector. J Urol 154:2170–2173. https://doi.org/10.1016/S0022-5347(01)66722-3
Nielsen MC, Martin-Bertelsen T, Friis M et al (2015) Differential gene expression in the otic capsule and the middle ear–an annotation of bone-related signaling genes. Otol Neurotol 36:727–732. https://doi.org/10.1097/MAO.0000000000000664
Noble BS, Stevens H, Loveridge N, Reeve J (1997) Identification of apoptotic changes in osteocytes in normal and pathological human bone. Bone 20:273–282. https://doi.org/10.1016/s8756-3282(96)00365-1
Parfitt AM (1994) Osteonal and hemi-osteonal remodeling: The spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273–286. https://doi.org/10.1002/jcb.240550303
Prentice AI (1967) Autofluorescence of bone tissues. J Clin Pathol 20:717–719. https://doi.org/10.1136/jcp.20.5.717
Riahi S, Noble B (2012) Techniques for the study of apoptosis in bone. Methods Mol Biol 816:335–349. https://doi.org/10.1007/978-1-61779-415-5_22
Sølvsten Sørensen M, Balslev Jørgensen M, Bretlau P (1992) Drift barriers in the postcartilaginous development of the mammalian otic capsule. Eur Arch Oto-Rhino-Laryngology 249:56–61. https://doi.org/10.1007/BF00175673
Sørensen MS (1994) Temporal bone dynamics, the hard way. Formation, growth, modeling, repair and quantum type bone remodeling in the otic capsule. Acta Otolaryngol Suppl 512:1–22
Sørensen MS, Bretlau P, Jørgensen MB (1990) Quantum type bone remodeling in the otic capsule of the pig. Acta Otolaryngol 110:217–223
Sørensen SS, Bretlau P, Jørgensen MB (1992) Quantum type bone remodeling in the human otic capsule: Morphometric findings. Acta Otolaryngol 112:4–10. https://doi.org/10.3109/00016489209136839
Tami A, Nasser P, Verborgt O et al (2002) The role of interstitial fluid flow in the remodeling response to fatigue and disuse. Am Soc Mech Eng Bioeng Div BED 50:335–336
Tiede-Lewis LAM, Xie Y, Hulbert MA et al (2017) Degeneration of the osteocyte network in the C57BL/6 mouse model of aging. Aging (Albany NY) 9:2187–2205. https://doi.org/10.18632/aging.101308
Vashishth D, Verborgt O, Divine G et al (2000) Decline in osteocyte lacunar density in human cortical bone is associated with accumulation of microcracks with age. Bone 26:375–380. https://doi.org/10.1016/S8756-3282(00)00236-2
Zehnder AF, Kristiansen AG, Adams JC et al (2005) Osteoprotegerin in the inner ear may inhibit bone remodeling in the otic capsule. Laryngoscope 115:172–177. https://doi.org/10.1097/01.mlg.0000150702.28451.35
Zehnder AF, Kristiansen AG, Adams JC et al (2006) Osteoprotegrin knockout mice demonstrate abnormal remodeling of the otic capsule and progressive hearing loss. Laryngoscope 116:201–206. https://doi.org/10.1097/01.mlg.0000191466.09210.9a
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hansen, L.J., Bloch, S.L. & Sørensen, M.S. Identification of Cellular Voids in the Human Otic Capsule. JARO 22, 591–599 (2021). https://doi.org/10.1007/s10162-021-00810-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10162-021-00810-6