Osteoprotegerin in the inner ear may inhibit bone remodeling in the otic capsule.
OBJECTIVE
To elucidate factors that may be responsible for the inhibition of remodeling of bone within the otic capsule.


METHODS
Expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK), and RANK ligand (RANKL) were assayed in samples of bone obtained from the otic capsule, calvarium, and femur, and from the soft tissue within the cochlea using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in mice. Immunostaining was used for histologic localization of the gene products. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the amount of OPG within perilymph, serum, and cerebrospinal fluid. The micro-anatomy of the interface between the otic capsule and the fluid spaces of the cochlea was investigated by brightfield and phase-contrast microscopy and by three-dimensional reconstruction in the mouse and human.


RESULTS
OPG, a powerful inhibitor of bone remodeling, was expressed at extremely high levels within the soft tissue of the cochlea and was present in the perilymph at very high concentrations. The OPG produced within the inner ear may diffuse into the surrounding otic capsule, where it may be responsible for inhibition of bone turnover. Our anatomic studies revealed an extensive system of interconnected canaliculi within the otic capsule that had direct openings into the fluid spaces of the inner ear, thus providing a possible anatomic route for the diffusion of OPG from the inner ear into the surrounding bone.


CONCLUSIONS
OPG, a potent inhibitor of osteoclast formation and function, is expressed at high levels within the inner ear and is secreted into the perilymph and the surrounding bone and may serve to inhibit active bone remodeling within the otic capsule, especially immediately adjacent to the cochlea. By this means, the cochlear soft tissue may control the nature of the surrounding petrous bone.
Zehnder
Andreas F
AF
Department of Otolaryngology, MA Eye and Ear Infirmary, and Harvard Medical School, Boston, MA, USA.
Kristiansen
Arthur G
AG
Adams
Joe C
JC
Merchant
Saumil N
SN
McKenna
Michael J
MJ
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis; D003051:Cochlea / Q000737:chemistry; D007758:Ear, Inner / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D053244:Osteoprotegerin; D010498:Perilymph / Q000737:chemistry; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000097:blood / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D013701:Temporal Bone / Q000737:chemistry*
D002352:Carrier Proteins; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse