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Identification of Cellular Voids in the Human Otic Capsule

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.

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References

  1. 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

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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

    Article  Google Scholar 

  3. 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

    Article  PubMed  Google Scholar 

  4. 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

    Article  PubMed  Google Scholar 

  5. 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

    Article  PubMed  Google Scholar 

  6. 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

    CAS  Article  Google Scholar 

  7. 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

    CAS  Article  PubMed  Google Scholar 

  8. 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

    Article  PubMed  Google Scholar 

  9. 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

    CAS  Article  Google Scholar 

  10. 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)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 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

    Article  PubMed  Google Scholar 

  12. 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

    Article  PubMed  Google Scholar 

  13. 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

    CAS  Article  PubMed  Google Scholar 

  14. 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

    CAS  Article  Google Scholar 

  15. Frost HM (1960a) Micropetrosis. J Bone Joint Surg Am 42 A:144–150. https://doi.org/10.2106/00004623-196042010-00012

  16. Frost HM (1960b) In vivo osteocyte death. J Bone Joint Surg Am 42-A:138–143

  17. Gundersen HJG (1986) Stereology of arbitrary particles. J Microsc 143:3–45. https://doi.org/10.1111/j.1365-2818.1986.tb02764.x

    CAS  Article  PubMed  Google Scholar 

  18. 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

    CAS  Article  Google Scholar 

  19. 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

    CAS  Article  Google Scholar 

  20. 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

    CAS  Article  PubMed  Google Scholar 

  21. Howard CV, Reed MG (2010) Unbiased Stereology. QTP Publications, Colerain, Second edi

    Google Scholar 

  22. 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

    CAS  Article  PubMed  Google Scholar 

  23. 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

    CAS  Article  PubMed  Google Scholar 

  24. Jilka RL, Noble B, Weinstein RS (2013) Osteocyte apoptosis. Bone 54:264–271. https://doi.org/10.1016/j.bone.2012.11.038

    Article  PubMed  Google Scholar 

  25. 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

    Article  PubMed  Google Scholar 

  26. 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

    CAS  Article  PubMed  Google Scholar 

  27. 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

    CAS  Article  PubMed  Google Scholar 

  28. 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

    Article  PubMed  Google Scholar 

  29. 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

    CAS  Article  PubMed  Google Scholar 

  30. 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

    CAS  Article  PubMed  Google Scholar 

  31. Prentice AI (1967) Autofluorescence of bone tissues. J Clin Pathol 20:717–719. https://doi.org/10.1136/jcp.20.5.717

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 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

    CAS  Article  PubMed  Google Scholar 

  33. 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

    Article  Google Scholar 

  34. 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

    PubMed  Google Scholar 

  35. Sørensen MS, Bretlau P, Jørgensen MB (1990) Quantum type bone remodeling in the otic capsule of the pig. Acta Otolaryngol 110:217–223

    Article  Google Scholar 

  36. 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

    Article  Google Scholar 

  37. 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

    Google Scholar 

  38. 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

  39. 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

    CAS  Article  PubMed  Google Scholar 

  40. 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

    CAS  Article  PubMed  Google Scholar 

  41. 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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Lars Juul Hansen.

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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

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