Osteoprotegerin in the Inner Ear May Inhibit Bone Remodeling in the Otic Capsule

Zehnder, Andreas; Kristiansen, Arthur G.; Adams, Joe C.; Merchant, Saumil N.; McKenna, Michael J.

doi:10.1097/01.mlg.0000150702.28451.35

Cited by 98 publications

(113 citation statements)

References 24 publications

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“…We recently found that expression of OPG also best characterizes the wild-type otic capsule (unpublished data). Our previous work showed that OPG plays an important role in the inhibition of otic capsule remod-eling [Zehnder et al, 2005], and that the otic capsule of the OPG knockout mice undergoes abnormal remodeling that closely resembles otosclerosis [Zehnder et al, 2006]. Because we did not observe active remodeling in the otic capsule of Mov13 mice, it is not surprising that expression levels of OPG remained high in the Mov13 otic capsule, thus contributing to the selection of OPG as a gene that is highly characteristic of the otic capsule.…”

Section: Discussionmentioning

confidence: 99%

Studies of Otic Capsule Morphology and Gene Expression in the Mov13 Mouse – An Animal Model of Type I Osteogenesis Imperfecta

Stanković

Kristiansen²,

Bizaki³

et al. 2007

Audiol Neurotol

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Type I osteogenesis imperfecta (OI) is a disorder of skeletal bones characterized by bone fragility and blue sclera, which can result from mutations in genes encoding for type I collagen – the COL1A1 and COL1A2 genes. Fifty percent of patients with type I OI develop hearing loss and associated histopathological changes in the otic capsule that are indistinguishable from otosclerosis, a major cause of acquired hearing loss. In an attempt to elucidate molecular and cellular mechanisms of hearing loss in type I OI, we have studied the Mov13 mouse, which has served as an animal model of type I OI by virtue of exhibiting variable transcriptional block of the COL1A1 gene. We studied the morphometry of the Mov13 otic capsule and compared expression levels of 60 genes in the otic capsule with those in the tibia and parietal bone of the Mov13 and wild-type mice. The degree of transcriptional block of the COL1A1 gene and its downstream effects differed significantly between the bones examined. We found that expression levels of bone morphogenetic protein 3 and nuclear factor ĸ-B1 best distinguished Mov13 otic capsule from wild-type otic capsule, and that osteoprotegerin, caspase recruitment domain containing protein 1, and partitioning defective protein 3 best distinguished Mov13 otic capsule from Mov13 tibia and parietal bone. Although the Mov13 mouse did not demonstrate evidence of active abnormal otic capsule remodeling as seen in type I OI and otosclerosis, studying gene expression in the Mov13 mouse has provided evidence that osteocytes of the otic capsule differ from osteocytes in other bones.

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Section: Discussionmentioning

confidence: 99%

Studies of Otic Capsule Morphology and Gene Expression in the Mov13 Mouse – An Animal Model of Type I Osteogenesis Imperfecta

Stanković

Kristiansen²,

Bizaki³

et al. 2007

Audiol Neurotol

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“…Bone remodeling within the otic capsule has been reported to be inhibited at or near the cochlea compared to the rest of the skeleton [Frisch et al, 1998[Frisch et al, , 2015Zehnder et al, 2005]. Zehnder et al [2005] demonstrated that osteoprotegerin (OPG), a powerful inhibitor of bone remodeling, was expressed at high levels within the soft tissue of the mouse cochlea and it was present in the perilymph at high concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…Zehnder et al [2005] demonstrated that osteoprotegerin (OPG), a powerful inhibitor of bone remodeling, was expressed at high levels within the soft tissue of the mouse cochlea and it was present in the perilymph at high concentrations. Bone remodeling is tightly regulated by 3 cytokines: OPG, receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL).…”

Section: Introductionmentioning

confidence: 99%

Evidence of Osteoclastic Activity in the Human Temporal Bone

Kamakura

Nadol²

2017

Audiol Neurotol

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Bone remodeling within the otic capsule has been reported to be inhibited especially at or near the cochlea, except under some pathological conditions such as otosclerosis, Paget's disease, or mastoiditis, when bone remodeling can occur. Microcavitations found in periosteal and endosteal layers of human temporal bone specimens without otosclerosis, Paget's disease, or inflammation as reported in the current study are consistent with osteoclastic bone resorption. Thirty-three temporal bones from 33 patients were prepared for light microscopy and classified into 4 groups: histologically proven dehiscence of the superior semicircular canal (SSCD) (n = 3, group 1), age 20 years or younger (n = 10, group 2), age 90 years or older and with otosclerosis (n = 10, group 3), and age 90 years or older without otosclerosis (n = 10, group 4). Microcavitation was seen at 7 anatomic locations in the temporal bone in all 4 groups, but not in the cochlea or vestibule. Microcavitation within the temporal bone is likely due to osteoclastic activity, and it is seen in both young and old patients, patients with and without otosclerosis, and in cases with SSCD.

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“…The RANK/RANKL/OPG signaling system that has recently been suggested to inhibit bone resorption and remodeling in the otic capsule [16,17] may act through the osteocytic lacunocanalicular network in perilabyrinthine bone [19] . Disruption of canaliculi and possibly even the osteocytic syncytium by MDx and larger microfissures might indeed interfere with signal transduction, counteract inhibiting signals and precipitate pathological bone remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…With the recognition of an inner ear signaling pathway [16,17] that inhibits perilabyrinthine bone remodeling to a mere 1% of the general rate [18] , otic capsular microfissures deserve renewed attention because these lesions are predicted by the virtual absence of bone remodeling and because they might disrupt the continuity of the lacunocanalicular porosity, affect the viability of the osteocytic network, interfere with perilabyrinthine antiresorptive signal transduction and consequently facilitate pathological capsular bone remodeling such as otosclerosis [19] .…”

Section: Introductionmentioning

confidence: 99%

Intravital Microlesions in the Human Otic Capsule

Frisch¹,

Bretlau²,

Sørensen³

2008

ORL

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Purpose of the Study: To verify microcracks in human temporal bones by a method which distinguishes intravital lesions from artifacts, to revisit previous information derived from decalcified materials on their morphology and classification and to discuss the possible clinical significance. Procedures: Histological analysis of 210 undecalcified adult human temporal bones bulk-stained by basic fuchsin in ethanol prior to embedding in methyl methacrylate and processing by the cutting and grinding method. Results: Intravital crack lesions appeared in all specimens and could be distinguished from artifacts regardless of crack morphology and size. Particularly, large microfissures were found around the labyrinthine windows, while smaller microfissures originating at the perilymphatic space were found throughout perilabyrinthine bone. Small noncommunicating fatigue microdamage was identified for the first time. All lesions were reorganized according to morphology, topography and possible clinical significance. Conclusion: Microfissures accumulate in the adult otic capsule as expected when bone remodeling is low. Any capsular microlesion may introduce a possible barrier in the recently discovered antiresorptive signaling pathway from inner ear structures via the lacunocanalicular osteocytic network to perilabyrinthine bone. For this reason intravital microfissures may interfere with in vivo inhibition of temporal bone remodeling and consequently offer another pathogenetic factor in otosclerosis.

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Osteoprotegerin in the Inner Ear May Inhibit Bone Remodeling in the Otic Capsule

Cited by 98 publications

References 24 publications

Studies of Otic Capsule Morphology and Gene Expression in the Mov13 Mouse – An Animal Model of Type I Osteogenesis Imperfecta

Studies of Otic Capsule Morphology and Gene Expression in the Mov13 Mouse – An Animal Model of Type I Osteogenesis Imperfecta

Evidence of Osteoclastic Activity in the Human Temporal Bone

Intravital Microlesions in the Human Otic Capsule

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