{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:54:03Z","timestamp":1789498443656,"version":"build-2803163510"},"reference-count":36,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/09034-0; 2017\/24073-8; 2013\/08216-2"],"award-info":[{"award-number":["2015\/09034-0; 2017\/24073-8; 2013\/08216-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>\n                    Osteoclasts play a key role in the regulation of bone mass and are highly active metabolically. Here we show that a metabolic reprogramming toward the hexosamine biosynthetic pathway (HBP) is required not only for osteoclast differentiation but also to determine the bone resorption mode during physiological and pathological bone remodeling. We found that pharmacological inhibition of O-GlcNAc transferase (OGT) significantly reduced protein O-GlcNAcylation and osteoclast differentiation. Accordingly, genetic deletion of OGT also inhibited osteoclast formation and downregulated critical markers related to osteoclasts differentiation and function (NFATc1, \u03b1\n                    <jats:sub>v<\/jats:sub>\n                    integrin, cathepsin K). Indeed, cells treated with OSMI-1, an OGT inhibitor, also reduced nuclear translocation of NFATc1. Furthermore, the addition of exogenous N-acetylglucosamine (GlcNAc) strongly increased osteoclast formation and demineralization ability. Strikingly, our data show for the first time that O-GlcNAcylation facilitates an aggressive trench resorption mode in human cells. The incubation of osteoclasts with exogenous GlcNAc increases the percentage of erosion by trench while having no effect on pit resorption mode. Through time-lapse recording, we documented that osteoclasts making trenches moving across the bone surface are sensitive to GlcNAcylation. Finally, osteoclast-specific Ogt-deficient mice show increased bone density and reduced inflammation-induced bone loss during apical periodontitis model. We show that osteoclast-specific Ogt-deficient mice are less susceptible to develop bacterial-induced periapical lesion. Consistent with this, Ogt-deleted mice showed a decreased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site. In summary, here we describe a hitherto undiscovered role of the HBP\/O-GlcNAcylation axis tuning resorption mode and dictating bone resorption outcome.\n                  <\/jats:p>","DOI":"10.1177\/00220345221141043","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T08:54:04Z","timestamp":1675760044000},"page":"440-449","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["HBP\/O-GlcNAcylation Metabolic Axis Regulates Bone Resorption Outcome"],"prefix":"10.1177","volume":"102","author":[{"given":"T.M.","family":"Taira","sequence":"first","affiliation":[{"name":"Department of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Avenida do Caf\u00e9, sn, 14040-903, Ribeir\u00e3o Preto, Brazil"},{"name":"Department of Pediatric, School of Dentistry of Ribeir\u00e3o Preto, Preventive and Social Dentistry, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, Brazil"},{"name":"Center for Research in Inflammatory Diseases, CRID, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900, casa 3, 14049-900, Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.S.","family":"Ramos-Junior","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Avenida do Caf\u00e9, sn, 14040-903, Ribeir\u00e3o Preto, Brazil"},{"name":"Department of Oral Biology & Diagnostic Sciences, The Dental College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.H.","family":"Melo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes, 3900, 14049-900, Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.C.","family":"Costa-Silva","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Avenida do Caf\u00e9, sn, 14040-903, Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.G.","family":"Alteen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, B.C. V5A 1S6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.J.","family":"Vocadlo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, B.C. V5A 1S6 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.B.","family":"Dias","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Glicobiologia Estrutural e Funcional, Centro de Ci\u00eancias da Sa\u00fade, Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. 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