{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T14:33:40Z","timestamp":1784385220516,"version":"3.55.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"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. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Osteoarthritis (OA) is a chronic degenerative joint disease characterized by articular cartilage loss and aberrant subchondral bone remodeling. \u201cT-cell immune regulator 1\u201d (<jats:italic>Tcirg1<\/jats:italic>), which encodes the a3 subunit of the V-ATPase, has been demonstrated to inhibit the formation of large osteoclasts by reducing intracellular calcium oscillations. Mutations in the <jats:italic>Tcirg1<\/jats:italic> gene sequence have been associated with osteopetrosis by impairing lysosomal transport in osteoclasts. This study aims to assess the impact of <jats:italic>Tcirg1<\/jats:italic> on OA progression and to explore its therapeutic potential for the disease treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Proteomic comparison of weight-bearing region (WBR) <jats:italic>versus<\/jats:italic> non-weight-bearing region (NWBR) of the subchondral bone was performed in 20 OA patients undergoing total knee arthroplasty. OA was then surgically induced in wild-type and Tcirg1-knockout mice by destabilization of the medial meniscus; disease severity and subchondral bone architecture were evaluated by histology and micro-CT. <jats:italic>In vitro<\/jats:italic>, primary bone marrow macrophages were differentiated into osteoclasts to assess the role of Tcirg1 in osteoclastogenesis, focusing on cell fusion, bone resorption, and lysosome acidification and distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Proteomic analysis revealed that TCIRG1 was significantly upregulated in the WBR compared to NWBR of subchondral bone in OA patients, with functional enrichment analysis indicating TCIRG1 correlation with lysosome-related biological processes. In the murine OA model, Tcirg1 expression increased in parallel with osteoclast activity, peaking at 4 weeks post-surgery, which coincided with severe subchondral bone loss. <jats:italic>Tcirg1<\/jats:italic> deficiency in knockout mice delayed OA progression, as evidenced by reduced cartilage damage, improved subchondral bone mass, and decreased osteoclast activity. <jats:italic>In vitro<\/jats:italic>, Tcirg1 expression increased during osteoclast differentiation, and its knockdown inhibited osteoclast fusion and bone resorption by impairing lysosome acidification and peripheral accumulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tcirg1 regulates lysosome acidification and peripheral accumulation, thereby influencing osteoclast activity in the subchondral bone. Given that <jats:italic>Tcirg1<\/jats:italic> knockdown was found to slow down the progression of OA, targeting Tcirg1 may serve as a potential therapeutic strategy for treating OA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1621648","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T05:26:18Z","timestamp":1757395578000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Tcirg1 deficiency delays osteoarthritis progression by impairing lysosome acidification and peripheral accumulation in osteoclasts"],"prefix":"10.3389","volume":"13","author":[{"given":"Rui","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaopu","family":"Tuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangbo","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuanmin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunhua","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/art.1780290816","article-title":"Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and therapeutic criteria committee of the American rheumatism association","volume":"29","author":"Altman","year":"1986","journal-title":"Arthritis Rheum."},{"key":"B2","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"7822","DOI":"10.4049\/jimmunol.178.12.7822","article-title":"Expression of the voltage-gated sodium channel NaV1.5 in the macrophage late endosome regulates endosomal acidification","volume":"178","author":"Carrithers","year":"2007","journal-title":"J. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"101842","DOI":"10.1016\/j.arr.2023.101842","article-title":"Physiological functions of podosomes: from structure and function to therapy implications in osteoclast biology of bone resorption","volume":"85","author":"Chen","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1080\/15548627.2024.2366748","article-title":"The different roles of V-ATPase a subunits in phagocytosis\/endocytosis and autophagy","volume":"20","author":"Chen","year":"2024","journal-title":"Autophagy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1177\/0363546517730072","article-title":"High rates of osteoarthritis develop after anterior cruciate ligament surgery: an analysis of 4108 patients","volume":"46","author":"Cinque","year":"2018","journal-title":"Am. J. Sports Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1177\/03635465231183088","article-title":"Markers of pain in 3 different murine models of posttraumatic osteoarthritis: a comparison using gait analysis, imaging, histology, and gene expression","volume":"51","author":"Croen","year":"2023","journal-title":"Am. J. Sports Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"ziae034","DOI":"10.1093\/jbmrpl\/ziae034","article-title":"Molecular and functional mapping of Plekhm1-Rab7 interaction in osteoclasts","volume":"8","author":"Das","year":"2024","journal-title":"JBMR Plus"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3892\/ijmm.2021.5059","article-title":"Dihydroartemisinin attenuates osteoclast formation and bone resorption via inhibiting the NF-\u03baB, MAPK and Nfatc1signaling pathways and alleviates osteoarthritis","volume":"49","author":"Ding","year":"2022","journal-title":"Int. J. Mol. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"6087","DOI":"10.1007\/s00018-021-03875-x","article-title":"Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune","volume":"78","author":"Dufran\u00e7ais","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5493","DOI":"10.1172\/JCI134091","article-title":"IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis","volume":"130","author":"Faust","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B12","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1042\/BJ20081073","article-title":"Atp6v1c1 is an essential component of the osteoclast proton pump and in F-actin ring formation in osteoclasts","volume":"417","author":"Feng","year":"2009","journal-title":"Biochem. J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/77131","article-title":"Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis","volume":"25","author":"Frattini","year":"2000","journal-title":"Nat. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e86330","DOI":"10.1172\/jci.insight.86330","article-title":"PLEKHM1\/DEF8\/RAB7 complex regulates lysosome positioning and bone homeostasis","volume":"1","author":"Fujiwara","year":"2016","journal-title":"JCI Insight"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.joca.2007.03.006","article-title":"The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129\/SvEv mouse","volume":"15","author":"Glasson","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"B16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/cells5030034","article-title":"Multiple roles of the small GTPase Rab7","volume":"5","author":"Guerra","year":"2016","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3892\/ijmm.2024.5410","article-title":"Unveiling the role of RhoA and ferroptosis in vascular permeability: implications for osteoarthritis","volume":"54","author":"He","year":"2024","journal-title":"Int. J. Mol. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1136\/annrheumdis-2020-218089","article-title":"Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis","volume":"80","author":"Hu","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1093\/rheumatology\/kew389","article-title":"What drives osteoarthritis? Synovial versus subchondral bone pathology","volume":"56","author":"H\u00fcgle","year":"2017","journal-title":"Rheumatol. Oxf. Engl. ."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","volume":"393","author":"Hunter","year":"2019","journal-title":"Osteoarthr. Lancet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4161\/sgtp.2.3.16453","article-title":"The regulation of osteoclast function and bone resorption by small GTPases","volume":"2","author":"Itzstein","year":"2011","journal-title":"Small GTPases"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e58599","DOI":"10.1371\/journal.pone.0058599","article-title":"RNAi-mediated silencing of Atp6i and Atp6i haploinsufficiency prevents both bone loss and inflammation in a mouse model of periodontal disease","volume":"8","author":"Jiang","year":"2013","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1431566","DOI":"10.3389\/fcell.2024.1431566","article-title":"Lysosomal biogenesis and function in osteoclasts: a comprehensive review","volume":"12","author":"Jiang","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"5178","DOI":"10.1182\/blood-2006-12-061382","article-title":"Hematopoietic stem cell-targeted neonatal gene therapy reverses lethally progressive osteopetrosis in Oc\/Oc mice","volume":"109","author":"Johansson","year":"2007","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1001\/jama.2020.22171","article-title":"Diagnosis and treatment of hip and knee osteoarthritis: a review","volume":"325","author":"Katz","year":"2021","journal-title":"JAMA"},{"key":"B26","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s41413-024-00326-8","article-title":"RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts","volume":"12","author":"Kim","year":"2024","journal-title":"Bone Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0140-6736(24)02322-5","volume":"405","author":"Kloppenburg","year":"2025","journal-title":"Osteoarthr. Lancet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2744","DOI":"10.4161\/cc.25825","article-title":"Regulation of lysosome biogenesis and functions in osteoclasts","volume":"12","author":"Lacombe","year":"2013","journal-title":"Cell Cycle"},{"key":"B29","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1136\/annrheumdis-2012-202989","article-title":"Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the osteoarthritis initiative","volume":"73","author":"Laslett","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1038\/nm1514","article-title":"V-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation","volume":"12","author":"Lee","year":"2006","journal-title":"Nat. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/70563","article-title":"Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification","volume":"23","author":"Li","year":"1999","journal-title":"Nat. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41413-018-0041-8","article-title":"Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12","volume":"7","author":"Lin","year":"2019","journal-title":"Bone Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"424","DOI":"10.2106\/00004623-197052030-00002","article-title":"Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips","volume":"52","author":"Mankin","year":"1970","journal-title":"J. Bone Jt. Surg. Am."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6701","DOI":"10.1038\/s41598-018-24918-7","article-title":"Essential role of the a3 isoform of V-ATPase in secretory lysosome trafficking via Rab7 recruitment","volume":"8","author":"Matsumoto","year":"2018","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.molcel.2014.11.006","article-title":"PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3\/GABARAP proteins","volume":"57","author":"McEwan","year":"2015","journal-title":"Mol. Cell."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1248\/bpb.b22-00371","article-title":"V-ATPase a3 subunit in secretory lysosome trafficking in osteoclasts","volume":"45","author":"Nakanishi-Matsui","year":"2022","journal-title":"Biol. Pharm. Bull."},{"key":"B37","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1136\/annrheumdis-2017-211811","article-title":"Effect of bisphosphonates on knee replacement surgery","volume":"77","author":"Neogi","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1042\/BST20180445","article-title":"Membrane trafficking in osteoclasts and implications for osteoporosis","volume":"47","author":"Ng","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"B39","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1158\/1541-7786.MCR-10-0449","article-title":"The a3 isoform vacuolar type H+-ATPase promotes distant metastasis in the mouse B16 melanoma cells","volume":"9","author":"Nishisho","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1002\/jbmr.355","article-title":"The V-ATPase a3 subunit mutation R740S is dominant negative and results in osteopetrosis in mice","volume":"26","author":"Ochotny","year":"2011","journal-title":"J. Bone Min. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"40050","DOI":"10.1074\/jbc.M106488200","article-title":"a4, a unique kidney-specific isoform of mouse vacuolar H+-ATPase subunit a","volume":"276","author":"Oka","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1016\/j.biocel.2012.05.014","article-title":"V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption","volume":"44","author":"Qin","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.1091\/mbc.E11-02-0155","article-title":"Vacuolar H(+)-ATPase subunits Voa1 and Voa2 cooperatively regulate secretory vesicle acidification, transmitter uptake, and storage","volume":"22","author":"Saw","year":"2011","journal-title":"Mol. Biol. Cell."},{"key":"B44","doi-asserted-by":"publisher","first-page":"eadk8544","DOI":"10.1126\/science.adk8544","article-title":"Molecular mechanism of dynein-dynactin complex assembly by LIS1","volume":"383","author":"Singh","year":"2024","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/nrendo.2013.137","article-title":"Osteopetrosis: genetics, treatment and new insights into osteoclast function","volume":"9","author":"Sobacchi","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1136\/annrheumdis-2014-206965","article-title":"Activated human B cells induce inflammatory fibroblasts with cartilage-destructive properties and become functionally suppressed in return","volume":"75","author":"St\u00f6rch","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1016\/j.joca.2010.06.007","article-title":"Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease","volume":"18","author":"Strassle","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4531","DOI":"10.1242\/jcs.03234","article-title":"The a3 isoform of V-ATPase regulates insulin secretion from pancreatic beta-cells","volume":"119","author":"Sun-Wada","year":"2006","journal-title":"J. Cell Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0002-9440(10)63798-4","article-title":"Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis","volume":"162","author":"Taranta","year":"2003","journal-title":"Am. J. Pathol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1080\/10985549.2024.2385633","article-title":"Unveiling the role of Sik1 in osteoblast differentiation: implications for osteoarthritis","volume":"44","author":"Tian","year":"2024","journal-title":"Mol. Cell. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1172\/JCI30328","article-title":"Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans","volume":"117","author":"Van Wesenbeeck","year":"2007","journal-title":"J. Clin. Invest."},{"key":"B52","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-pathmechdis-031521-040919","article-title":"Osteoclasts, master sculptors of bone","volume":"18","author":"Veis","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/jbmr.1727","article-title":"The R740S mutation in the V-ATPase a3 subunit increases lysosomal pH, impairs NFATc1 translocation, and decreases in vitro osteoclastogenesis","volume":"28","author":"Voronov","year":"2013","journal-title":"J. Bone Min. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1083\/jcb.201312109","article-title":"Ca2+-calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via V-ATPase subunit V0a1","volume":"205","author":"Wang","year":"2014","journal-title":"J. Cell Biol."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3791\/62718","article-title":"Tissue collection and RNA extraction from the human osteoarthritic knee joint","volume":"173","author":"Wilson","year":"2021","journal-title":"J. Vis. Exp."},{"key":"B56","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/s41591-024-02822-0","article-title":"RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial","volume":"30","author":"Wittoek","year":"2024","journal-title":"Nat. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.tcb.2019.02.004","article-title":"Regulation and function of mitochondria-lysosome membrane contact sites in cellular homeostasis","volume":"29","author":"Wong","year":"2019","journal-title":"Trends Cell Biol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1080\/15548627.2019.1569916","article-title":"The macrophage-specific V-ATPase subunit ATP6V0D2 restricts inflammasome activation and bacterial infection by facilitating autophagosome-lysosome fusion","volume":"15","author":"Xia","year":"2019","journal-title":"Autophagy"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e27285","DOI":"10.1371\/journal.pone.0027285","article-title":"LIS1 regulates osteoclast formation and function through its interactions with dynein\/dynactin and Plekhm1","volume":"6","author":"Ye","year":"2011","journal-title":"PLOS One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.7150\/ijbs.15583","article-title":"LIS1 regulates osteoclastogenesis through modulation of M-SCF and RANKL signaling pathways and CDC42","volume":"12","author":"Ye","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.bone.2015.02.017","article-title":"Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-\u03baB and PI3K\/Akt signaling pathways","volume":"75","author":"Yuan","year":"2015","journal-title":"Bone"},{"key":"B62","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1074\/jbc.M708058200","article-title":"V-ATPase V0 sector subunit a1 in neurons is a target of calmodulin","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B63","doi-asserted-by":"publisher","first-page":"e0237354","DOI":"10.1371\/journal.pone.0237354","article-title":"Knockdown of Tcirg1 inhibits large-osteoclast generation by down-regulating Nfatc1and IP3R2 expression","volume":"15","author":"Zhang","year":"2020","journal-title":"PLOS One"},{"key":"B64","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/nm.3143","article-title":"Inhibition of TGF-\u03b2 signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis","volume":"19","author":"Zhen","year":"2013","journal-title":"Nat. Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1172\/JCI121561","article-title":"Subchondral bone osteoclasts induce sensory innervation and osteoarthritis pain","volume":"129","author":"Zhu","year":"2019","journal-title":"J. Clin. Invest."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1621648\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T05:26:20Z","timestamp":1757395580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1621648\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":65,"alternative-id":["10.3389\/fcell.2025.1621648"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1621648","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,9]]},"article-number":"1621648"}}