{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T08:16:59Z","timestamp":1775117819594,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Bone tuberculosis is characterized by severe bone destruction driven by aberrant osteoclast overactivation. However, the direct mechanism by which Mycobacterium tuberculosis (Mtb) mediates this pathological process remains unclear. Understanding the molecular basis of pathogen-driven osteoclast dysregulation is essential for developing effective host-directed therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic profiling was performed to identify differentially expressed sialylation-related genes and activated signaling pathways in Mtb-infected cells. Murine bone-tuberculosis models and in vitro osteoclast cultures were employed to assess osteoclast activity and surface \u03b12,3-sialylation levels following Mtb infection. Functional interventions included enzymatic removal of \u03b12,3-sialic acid and pharmacological inhibition of ST3GAL1. Metabolomic analysis was conducted to characterize Mtb-induced alterations in glycerophospholipid metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic profiling revealed upregulation of sialylation-related genes and activation of TLR2-dependent signaling upon Mtb infection, providing a molecular basis for pathogen-driven surface glycan modifications. In both murine bone-tuberculosis models and in vitro osteoclast cultures, Mtb infection concurrently enhanced osteoclast activity and surface \u03b12,3-sialylation. Enzymatic desialylation or ST3GAL1 inhibition markedly attenuated this overactivation. Metabolomic analysis further demonstrated Mtb-induced reprogramming of glycerophospholipid metabolism, potentially supplying substrates for sialylated glycoconjugate biosynthesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify \u03b12,3-sialylation as a central driver of Mtb-induced pathological osteoclast activity, mechanistically linking TLR2 signaling, surface glycan remodeling, and metabolic reprogramming. The coordinate regulation of membrane glycoconjugate biosynthesis and glycerophospholipid metabolism suggests an integrated host response exploited by Mtb to promote bone destruction. Collectively, host glycosylation machinery and associated metabolic pathways represent promising targets for host-directed therapy in bone tuberculosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1738896","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:43:03Z","timestamp":1775115783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mycobacterium tuberculosis infection drives osteoclast overactivation via \u03b12,3-Sialylation to promote pathological bone destruction"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiwei","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qixiu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiezhong","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuquan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ce","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4045","DOI":"10.1021\/acs.jproteome.7b00429","article-title":"N\u03b5- and O-Acetylation in Mycobacterium tuberculosis lineage 7 and lineage 4 strains: proteins involved in bioenergetics, virulence, and antimicrobial resistance are acetylated","volume":"16","author":"Birhanu","year":"2017","journal-title":"J. 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