{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:27:21Z","timestamp":1761006441128,"version":"build-2065373602"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002582","name":"American Geriatrics Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002582","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010836","name":"American Laryngological, Rhinological and Otological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Identify and compare phenotypic properties of osteoblasts from patients with otosclerosis (OSO), normal bones (HOB), and normal stapes (NSO) to determine a possible cause for OSO hypermineralization and assess any effects of the bisphosphonate, alendronate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>OSO (n = 11), NSO (n = 4), and HOB (n = 13) cultures were assayed for proliferation, adhesion, mineralization, and gene expression with and without 10<jats:sup>\u201310<\/jats:sup>M\u201010<jats:sup>\u20138<\/jats:sup>M alendronate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Academic hospital.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cultures were matched for age, sex, and passage number. Cell attachment and proliferation + alendronate were determined by Coulter counting cells and assaying tritiated thymidine uptake, respectively. At 7, 14, and 21\u00a0days of culture + alendronate, calcium content and gene expression by quantitative reverse transcription\u2010polymerase chain reaction (qRT\u2010PCR) were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OSO had significantly more cells adhere but less proliferation than NSO or HOB. Calcification was significantly increased in OSO compared to HOB and NSO. NSO and HOB had similar cell adhesion and proliferation rates. A dose\u2010dependent effect of alendronate on OSO adhesion, proliferation, and mineralization was found, resulting in levels equal to NSO and HOB. All cultures expressed osteoblast\u2010specific genes such as RUNX2, alkaline phosphatase, type I collagen, and osteocalcin. However, osteopontin was dramatically reduced, 9.4\u2010fold at 14\u00a0days, in OSO compared to NSO. Receptor activator of nuclear factor \u03baB ligand\/osteoprotegerin (RANKL\/OPG), important in bone resorption, was elevated in OSO with decreased levels of OPG levels. Alendronate had little effect on gene expression in HOB but in OSO increased osteopontin levels and decreased RANKL\/OPG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>OSO cultures displayed properties of hypermineralization due to decreased osteopontin (OPN) and also had increased RANKL\/OPG, which were normalized by alendronate.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599814544889","type":"journal-article","created":{"date-parts":[[2014,8,2]],"date-time":"2014-08-02T05:00:01Z","timestamp":1406955601000},"page":"657-666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differences in Otosclerotic and Normal Human Stapedial Osteoblast Properties Are Normalized by Alendronate in Vitro"],"prefix":"10.1002","volume":"151","author":[{"given":"Gloria","family":"Gronowicz","sequence":"first","affiliation":[{"name":"University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne L.","family":"Richardson","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Flynn","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Kveton","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Eisen","sequence":"additional","affiliation":[{"name":"Hartford Hospital Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Leonard","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Aronow","sequence":"additional","affiliation":[{"name":"Hartford Hospital Hartford Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Rodner","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kourosh","family":"Parham","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"162","article-title":"Does otosclerosis occur only in the temporal bone?","volume":"20","author":"Wang PC","year":"1999","journal-title":"Am J Otol"},{"key":"e_1_2_9_3_1","first-page":"426","article-title":"The genetics of otosclerosis: a review","volume":"10","author":"Gordon MA","year":"1989","journal-title":"Am J Otol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200103000-00023"},{"key":"e_1_2_9_5_1","first-page":"249","article-title":"Current research in otosclerosis","volume":"22","author":"Stankovic K","year":"2006","journal-title":"Otol Neurotol"},{"key":"e_1_2_9_6_1","first-page":"86","article-title":"Measles virus and otosclerosis","volume":"65","author":"Niedermeyer HP","year":"2007","journal-title":"Adv Otorhinolaryngol"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348943304200209"},{"key":"e_1_2_9_8_1","first-page":"365","volume-title":"Pathology of the Ear","author":"Schuknecht H","year":"1993"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.12.7852"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2005.00441.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1962.00740050208004"},{"key":"e_1_2_9_12_1","unstructured":"MugnierA.Embryologie et D\u00e9veloppement Bucco\u2010 Facial Paris: Masson.1964."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0709(87)80051-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000191466.09210.9a"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/000164802321040964"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200311000-00005"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000231733.02481.59"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e318164d12c"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335098"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.277.6.E1005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(03)00155-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/019459989310900312"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e318268d1b3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/014556139707600605"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080812"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-006-0168-2"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2003.09.005"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.12.001"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1700451"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00129492-200301000-00010"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(97)80155-X"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90115-S"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00971-6"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410100417"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.4146"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.104.4.1013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/35.7.3295029"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.12.4473"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(95)00046-7"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008209609029192"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-001-1121-z"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.1.426"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-6009(08)80225-5"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(00)00108-6"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3109\/00313028409067908"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2010.02.007"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-010-1404-y"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2008.03.001"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2008.07.001"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1067\/mlc.2000.109757"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2005.04.059"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2003.11.024"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.02.023"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-011-9473-5"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.31336"}],"container-title":["Otolaryngology\u2013Head and Neck Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0194599814544889","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1177\/0194599814544889","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aao-hnsfjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0194599814544889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:51:43Z","timestamp":1760950303000},"score":1,"resource":{"primary":{"URL":"https:\/\/aao-hnsfjournals.onlinelibrary.wiley.com\/doi\/10.1177\/0194599814544889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1177\/0194599814544889"],"URL":"https:\/\/doi.org\/10.1177\/0194599814544889","archive":["Portico"],"relation":{},"ISSN":["0194-5998","1097-6817"],"issn-type":[{"type":"print","value":"0194-5998"},{"type":"electronic","value":"1097-6817"}],"subject":[],"published":{"date-parts":[[2014,8]]},"assertion":[{"value":"2014-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}