{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:35:54Z","timestamp":1778837754791,"version":"3.51.4"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[1994,10,1]],"date-time":"1994-10-01T00:00:00Z","timestamp":780969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DE 05996"],"award-info":[{"award-number":["DE 05996"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Finnish Academy and the Finnish Dental"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It has been shown that a specific inhibitor of vacuolar H+-ATPases, bafilomycin A1, inhibits bone resorption by isolated chicken osteoclasts by blocking the proton pump in the ruffled border membrane. We report here the effects of bafilomycin A1 on bone resorption in vivo. Using a cannulated osmotic minipump delivery system, we infused bafilomycin locally to the eruption pathway of permanent premolars of beagle dogs. We used pit formation by osteoclasts in vitro to estimate the concentrations and heat stability of bafilomycin to be used in vivo. In this model, osteoclasts were cultured on thin bone slices, in which they form pits indicative of resorption. After 2 weeks preincubation at 37\u00b0C, bafilomycin concentrations of 10\u22126 and 10\u22127 M but not 10\u22128 M completely inhibited the resorptive activity of cultured osteoclasts, and the two larger doses were chosen for use in vivo. Local delivery of 10\u22126 M bafilomycin to the eruption pathway of the fourth permanent mandibular premolar during mideruption inhibited tooth eruption by blocking bone resorption as assayed by radiography, light microscopy, and scanning electron microscopy. Bafilomycin at 10\u22127 M had similar but less intensive effects. Moreover, osteoclasts in the alveolar bone of crypts treated with 10\u22127 M bafilomycin A1 stained very weakly for tartrate-resistant acid phosphatase. The effect of bafilomycin on bone resorption was shown to be very local, and no side effects of treatment with bafilomycin were observed in adjacent teeth or the behavior of dogs. We report here, for the first time, inhibition of tooth eruption caused by inhibited bone resorption using bafilomycin A1 in vivo.<\/jats:p>","DOI":"10.1002\/jbmr.5650091010","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:27:42Z","timestamp":1265214462000},"page":"1575-1582","source":"Crossref","is-referenced-by-count":42,"title":["Bafilomycin A1 inhibits bone resorption and tooth eruption in vivo"],"prefix":"10.1093","volume":"9","author":[{"given":"Kai T.","family":"Sundquist","sequence":"first","affiliation":[{"name":"University of Massachusetts Medical School, Department of Cell Biology, Worcester, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Sandy C.","family":"Marks","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School, Department of Cell Biology, Worcester, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1994,10,1]]},"reference":[{"key":"2024013113133714300_bib1","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1083\/jcb.101.6.2210","article-title":"Cell-mediated extracellular acidification and bone resorption: Evidence for a low pH in resorbing lacunae and localication of a 100-kD lysosomal membrane protein at the osteoclast ruffled border","volume":"101","author":"Baron","year":"1985","journal-title":"J Cell Biol"},{"key":"2024013113133714300_bib2","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1126\/science.2528207","article-title":"Osteoclast bone resorption by a polarized vacuolar proton pump","volume":"245","author":"Blair","year":"1989","journal-title":"Science"},{"key":"2024013113133714300_bib3","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1083\/jcb.111.3.1305","article-title":"Evidence for the presence of a proton pump of the vacuolar H+ -type in the ruffled borders of osteoclasts","volume":"111","author":"V\u00e4\u00e4n\u00e4nen","year":"1990","journal-title":"J Cell Biol"},{"key":"2024013113133714300_bib4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/jbmr.5650080115","article-title":"Proton channel part of vacuolar H+ -ATPase and carbonic anhydrase II expression is stimulated in resorbing osteoclasts","volume":"8","author":"Laitala","year":"1993","journal-title":"J Bone Miner Res"},{"key":"2024013113133714300_bib5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/BF00808113","article-title":"Structure, molecular genetics, and evolution of vacuolar H+-ATPases","volume":"21","author":"Nelson","year":"1989","journal-title":"J Bioenerg Biomembr"},{"key":"2024013113133714300_bib6","doi-asserted-by":"crossref","first-page":"15780","DOI":"10.1016\/S0021-9258(18)47797-6","article-title":"Immunoaffinity purification and characterization of vacuolar H+-ATPase from bovine kidney","volume":"262","author":"Gluck","year":"1987","journal-title":"J Biol Chem"},{"key":"2024013113133714300_bib7","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1172\/JCI111378","article-title":"An electrogenic proton-translocating adenosine triphosphatase from bovine kidney medulla","volume":"73","author":"Gluck","year":"1984","journal-title":"J Clin Invest"},{"key":"2024013113133714300_bib8","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/0955-0674(92)90086-R","article-title":"Organellar proton-ATPases","volume":"4","author":"Nelson","year":"1992","journal-title":"Curr Opin Cell Biol"},{"key":"2024013113133714300_bib9","doi-asserted-by":"crossref","first-page":"6257","DOI":"10.1073\/pnas.89.14.6257","article-title":"Sensitivity to vanadate and isoforms of subunits A and B distinguish the osteoclast proton pump from other vacuolar H+ ATPases","volume":"89","author":"Chatterjee","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113133714300_bib10","doi-asserted-by":"crossref","first-page":"110","DOI":"10.7164\/antibiotics.37.110","article-title":"Metabolic products of microorganisms. Bafilomycin, a new group of macrolide antibiotics production, isolation, chemical structure and biological activity","volume":"37","author":"Werner","year":"1984","journal-title":"J Antibiot"},{"key":"2024013113133714300_bib11","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/0006-291X(90)91709-2","article-title":"Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption","volume":"168","author":"Sundquist","year":"1990","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013113133714300_bib12","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1006\/bbrc.1993.1783","article-title":"Purification of vacuolar ATPase with bafilomycin C1 affinity chromatography","volume":"194","author":"Rautiala","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013113133714300_bib13","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0096-6347(41)90413-1","article-title":"Studies in tooth development theories of eruption","volume":"27","author":"Massler","year":"1941","journal-title":"Am J Orthodont Oral Surg"},{"key":"2024013113133714300_bib14","first-page":"92","volume-title":"Biology of the Periodontium","author":"Ten Cate","year":"1969"},{"key":"2024013113133714300_bib15","first-page":"215","volume-title":"The Periodontal Ligament in Health and Disease","author":"Moxham","year":"1982"},{"key":"2024013113133714300_bib16","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1177\/10454411920030030201","article-title":"Current concepts of the biology of tooth eruption","volume":"3","author":"Gorski","year":"1992","journal-title":"Crit Rev Oral Biol Med."},{"key":"2024013113133714300_bib17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/ar.1091640105","article-title":"Eruption pathway formation in the presence of experimental tooth impaction in puppies","volume":"164","author":"Cahill","year":"1969","journal-title":"Anat Rec"},{"key":"2024013113133714300_bib18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1600-0714.1980.tb00377.x","article-title":"Tooth eruption: Evidence for the central role of the dental follicle","volume":"9","author":"Cahill","year":"1980","journal-title":"J Oral Pathol"},{"key":"2024013113133714300_bib19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/jmor.1051710208","article-title":"Chronology and histology of exfoliation and eruption of mandibular premolars in dogs","volume":"171","author":"Cahill","year":"1982","journal-title":"J Morphol"},{"key":"2024013113133714300_bib20","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/j.1600-0714.1988.tb01324.x","article-title":"Local infusion of prostaglandin E1 stimulates mandibular bone formation in vivo","volume":"17","author":"Marks","year":"1988","journal-title":"J Oral Pathol"},{"key":"2024013113133714300_bib21","first-page":"375","author":"Marks","year":"1991"},{"key":"2024013113133714300_bib22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/aja.1001680303","article-title":"The cytology of the dental follicle and adjacent alveolar bone during tooth eruption","volume":"168","author":"Marks","year":"1983","journal-title":"Am J Anat"},{"key":"2024013113133714300_bib23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1177\/35.2.3540104","article-title":"Tartrate-resistant acid phosphatase in bone and cartilage following decalcification and cold-embedding in plastic","volume":"35","author":"Cole","year":"1987","journal-title":"J Histochem Cytochem"},{"key":"2024013113133714300_bib24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1242\/jcs.57.1.247","article-title":"Osteoblasts release osteoclasts from calsitonin-induced quiescence","volume":"57","author":"Chambers","year":"1982","journal-title":"J Cell Sci"},{"key":"2024013113133714300_bib25","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/sj.bdj.4805313","article-title":"Resorption of dentine by isolated osteoclats in vitro","volume":"156","author":"Boyde","year":"1984","journal-title":"Br Dent J"},{"key":"2024013113133714300_bib26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0005-2736(91)90238-4","article-title":"Omeprazole and bafilomycin, two proton pump inhibitors: Differentiation of their effects on gastric, kidney and bone H+-translocating ATPases","volume":"1065","author":"Mattsson","year":"1991","journal-title":"Biochim Biophys Acta"},{"key":"2024013113133714300_bib27","doi-asserted-by":"crossref","first-page":"7972","DOI":"10.1073\/pnas.85.21.7972","article-title":"Bafilomycins: A class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells","volume":"85","author":"Bowman","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113133714300_bib28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0005-2760(92)90214-G","article-title":"Inhibition of the accumulation of lipid droplets in macrophage J774 by bafilomycin B1 and destruxin E","volume":"1126","author":"Naganuma","year":"1992","journal-title":"Biochim Biophys Acta"},{"key":"2024013113133714300_bib29","doi-asserted-by":"crossref","first-page":"17707","DOI":"10.1016\/S0021-9258(19)47429-2","article-title":"Bafilomycin A1, a specific inhibitor of vacuolar-type H+ -ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells","volume":"266","author":"Yoshimori","year":"1991","journal-title":"J Biol Chem"},{"key":"2024013113133714300_bib30","first-page":"S64","article-title":"Biochemical aspects of H+-ATPase in renal proximal tubules: Inhibition by N,N'-dicyclohexylcarbodiimide, N-ethylmaleimide, and bafilomycin","volume":"33","author":"Jehmlich","year":"1991","journal-title":"Kidney Int (Suppl)"},{"key":"2024013113133714300_bib31","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/1523-1747.ep12470970","article-title":"Vacuolar acidification and bafilomycin-sensitive proton translocating ATPase in human epidermal Lengerhans cells","volume":"96","author":"Girolomoni","year":"1991","journal-title":"J Invest Dermatol"},{"key":"2024013113133714300_bib32","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/0006-291X(90)92172-V","article-title":"Kinetic studies of chromaffin granule H+-ATPase and effects of bafilomycin A1","volume":"170","author":"Hanada","year":"1990","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013113133714300_bib33","first-page":"1125","article-title":"Tooth eruption: The regulation of a localized, bilaterally symmetrical metabolic event in alveolar bone","volume":"1","author":"Marks","year":"1987","journal-title":"Scanning Microsc"},{"key":"2024013113133714300_bib34","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0006-291X(89)92405-4","article-title":"Inhibition of osteoclastic acid phosphatase abolishes bone resorption","volume":"159","author":"Zaidi","year":"1989","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013113133714300_bib35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/BF02441189","article-title":"Purification and partial characterization of two acid phosphatases from rat bone","volume":"27","author":"Anderson","year":"1979","journal-title":"Calcif Tissue Int"},{"key":"2024013113133714300_bib36","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/jcp.1041320112","article-title":"Hormonal regulation of acid phosphatase release by osteoclasts disaggregated from neonatal rat bone","volume":"132","author":"Chambers","year":"1987","journal-title":"J Cell Physiol"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.5650091010","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/9\/10\/1575\/56494545\/5650091010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/9\/10\/1575\/56494545\/5650091010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:59:18Z","timestamp":1710341958000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/9\/10\/1575-1582\/7500330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,10,1]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[1994,10,1]]},"published-print":{"date-parts":[[1994,10,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650091010","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1994,10,1]]},"published":{"date-parts":[[1994,10,1]]}}}