{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:26:22Z","timestamp":1793363182344,"version":"4.5.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100955"],"award-info":[{"award-number":["82100955"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271013"],"award-info":[{"award-number":["82271013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M692429"],"award-info":[{"award-number":["2021M692429"]}],"id":[{"id":"10.13039\/501100002858","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":[[2026,5]]},"abstract":"<jats:p>\n                    While the biological functions and molecular mechanisms of osteoclasts in condylar morphogenesis remain incompletely characterized, and the regulatory effects of hypoxic conditions within the deep condyle on osteoclast-mediated alveolar bone remodeling are poorly understood, this investigation systematically examines the hypoxia response mechanisms of cathepsin K\u2013positive (ctsk\n                    <jats:sup>+<\/jats:sup>\n                    ) osteoclasts and their specialized functions in condylar tissue organization. Genetic ablation of ctsk+ cells in diphtheria toxin receptor (DTR) transgenic mice resulted in pronounced accumulation of calcified cartilage within the mandibular condylar cartilage (MCC) accompanied by impaired subchondral bone formation\u2014phenotypes directly attributable to osteoclast deficiency. Intriguingly, DTR animals exhibited concurrent upregulation of chondroblast markers, osteoblastic factors, and bone resorption mediators, suggesting that ctsk+ cells normally function to restrain MCC proliferation and premature hypertrophy while simultaneously inhibiting subchondral osteogenesis. Conditional knockout of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) specifically in ctsk+ cells (HIF-1\u03b1\n                    <jats:sup>\u2206ctsk-cre<\/jats:sup>\n                    ) replicated the cartilage accumulation phenotype observed in DTR mice during early development (\u22645\u2009wk), with comparable disorganization of the fibrocartilage layers. However, after 6\u2009wk, HIF-1\u03b1\n                    <jats:sup>\u2206ctsk-cre<\/jats:sup>\n                    mutants displayed paradoxical cartilage reduction coupled with accelerated subchondral mineralization. We propose that progressive osteoclast depletion, combined with extensive chondrocyte apoptosis and elevated matrix metalloproteinase 13 expression, drives the gradual MCC thinning in knockout animals. The sustained osteoclast deficiency appears to disrupt the physiological cartilage-to-bone transition, ultimately causing delayed but exaggerated subchondral mineralization. At the cellular level, HIF-1\u03b1 deficiency in ctsk+ osteoclasts induced profound structural abnormalities, including disorganized ruffled borders and defective lysosomal biogenesis. Mechanistically, we identified the osteoclast-specific TSC2-mTORC1-TFEB axis as a critical regulator of hypoxia-responsive lysosomal formation. Collectively, these findings establish a novel dual regulatory role for ctsk+ cells: suppressing chondrocyte proliferation, premature hypertrophy, and osteogenesis through bone resorption signaling and mediating HIF-1\u03b1\u2013dependent control of osteoclastogenesis and lysosomal function during calcified cartilage degradation.\n                  <\/jats:p>","DOI":"10.1177\/00220345251369411","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T08:41:28Z","timestamp":1760776888000},"page":"626-636","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Ctsk\n                    <sup>+<\/sup>\n                    Osteoclasts Orchestrate Condylar Morphogenesis via Hypoxic Lysosome"],"prefix":"10.1177","volume":"105","author":[{"given":"Y.","family":"Tang","sequence":"first","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Periodontology, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bie","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Oral and Maxillofacial Surgery, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China"},{"name":"Department of Second Dental Center, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University; School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Oral and Maxillofacial Surgery, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Cong","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration and Regeneration &amp; Tongji Research Institute of Stomatology &amp; Department of Oral and Maxillofacial Surgery, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of Tooth Restoration 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