{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:36:56Z","timestamp":1784763416917,"version":"3.55.0"},"reference-count":138,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21AR082401"],"award-info":[{"award-number":["R21AR082401"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our understanding of the different developmental origins of osteoclast progenitors and their respective roles during homeostatic bone remodeling at different skeletal sites as well as their roles within bone regeneration and degenerative conditions is evolving. In this narrative review article, we summarize what is known about the developmental origins, anatomical sources, and markers of osteoclast progenitors. We touch on how osteoclast progenitors vary during different disease contexts, including periodontitis, rheumatoid arthritis, and osteoarthritis. In addition, we also characterize osteoclast progenitors that contribute to bone healing and define changes observed with advancing age. In this regard, we offer a critical review of gaps within our understanding and opportunities for future development within the field. Because of their diverse nature under different contexts, identifying and characterizing osteoclast progenitors may help to advance condition-specific therapies.<\/jats:p>","DOI":"10.3390\/ijms262110619","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Development, Disease, and Decline: A Review of What Defines an Osteoclast Progenitor"],"prefix":"10.3390","volume":"26","author":[{"given":"Mitchell J.","family":"Shimak","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9228-647X","authenticated-orcid":false,"given":"Ismael Y.","family":"Karkache","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Comparative and Molecular Biosciences, School of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth K.","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Chavez","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Manser","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archisha","family":"Basak","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng Cha","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsha","family":"Koroth","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-5524","authenticated-orcid":false,"given":"Elizabeth W.","family":"Bradley","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Stem Cell Institute, Medical School, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sarafrazi, N., Wambogo, E.A., and Shepherd, J.A. (2021). Osteoporosis or Low Bone Mass in Older Adults: United States, 2017\u20132018. NCHS Data Brief, 1\u20138.","DOI":"10.15620\/cdc:103477"},{"key":"ref_2","first-page":"9","article-title":"Primary osteoporosis in postmenopausal women","volume":"1","author":"Ji","year":"2015","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1001\/jamainternmed.2019.0682","article-title":"Association of Disease Definition, Comorbidity Burden, and Prognosis With Hip Fracture Probability Among Late-Life Women","volume":"179","author":"Ensrud","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1007\/s00198-017-4153-6","article-title":"Costs of fragility hip fractures globally: A systematic review and meta-regression analysis","volume":"28","author":"Williamson","year":"2017","journal-title":"Osteoporos. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/jbmr.4821","article-title":"Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality","volume":"38","author":"Sing","year":"2023","journal-title":"J. Bone Miner. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1291","DOI":"10.5435\/JAAOS-D-22-00273","article-title":"AAOS Clinical Practice Guideline Summary: Management of Hip Fractures in Older Adults","volume":"30","author":"Switzer","year":"2022","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Goodman, S.B., and Gallo, J. (2019). Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122091"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hodges, N.A., Sussman, E.M., and Stegemann, J.P. (2021). Aseptic and septic prosthetic joint loosening: Impact of biomaterial wear on immune cell function, inflammation, and infection. Biomaterials, 278.","DOI":"10.1016\/j.biomaterials.2021.121127"},{"key":"ref_9","unstructured":"GBD 2019 Fracture Collaborators (2021). Global, regional, and national burden of bone fractures in 204 countries and territories, 1990\u20132019: A systematic analysis from the Global Burden of Disease Study 2019. Lancet Healthy Longev., 2, e580\u2013e592."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Coury, F., Peyruchaud, O., and Machuca-Gayet, I. (2019). Osteoimmunology of Bone Loss in Inflammatory Rheumatic Diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00679"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115403","DOI":"10.1016\/j.bone.2020.115403","article-title":"What do we know about bone morphogenetic proteins and osteochondroprogenitors in inflammatory conditions?","volume":"137","author":"Lukac","year":"2020","journal-title":"Bone"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1056\/NEJMra2103726","article-title":"Rheumatoid Arthritis\u2014Common Origins, Divergent Mechanisms","volume":"388","author":"Gravallese","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhou, M., and Graves, D.T. (2022). Impact of the host response and osteoblast lineage cells on periodontal disease. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.998244"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25103","DOI":"10.1074\/jbc.R109.041087","article-title":"Cellular and molecular mechanisms of bone remodeling","volume":"285","author":"Raggatt","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/jbmr.4773","article-title":"Macrophages and Bone Remodeling","volume":"38","author":"Weivoda","year":"2023","journal-title":"J. Bone Miner. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e202411024","DOI":"10.1083\/jcb.202411024","article-title":"Mechanical control of osteoclast fusion by membrane-cortex attachment and BAR proteins","volume":"224","author":"Wan","year":"2025","journal-title":"J. Cell. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4068\/cmj.2016.52.1.12","article-title":"Signaling Pathways in Osteoclast Differentiation","volume":"52","author":"Kim","year":"2016","journal-title":"Chonnam Med. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s00441-010-1086-1","article-title":"Osteoblast physiology in normal and pathological conditions","volume":"343","author":"Neve","year":"2011","journal-title":"Cell Tissue Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/0004563218759371","article-title":"The bone remodelling cycle","volume":"55","author":"Kenkre","year":"2018","journal-title":"Ann. Clin. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/bonekey.2014.56","article-title":"The reversal phase of the bone-remodeling cycle: Cellular prerequisites for coupling resorption and formation","volume":"3","author":"Delaisse","year":"2014","journal-title":"Bonekey Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.cell.2021.02.002","article-title":"Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption","volume":"184","author":"McDonald","year":"2021","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.4049\/jimmunol.181.2.1232","article-title":"Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo","volume":"181","author":"Chang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1002\/eji.1830111013","article-title":"F4\/80, a monoclonal antibody directed specifically against the mouse macrophage","volume":"11","author":"Austyn","year":"1981","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S8756-3282(00)00306-9","article-title":"Osteoclast lineage commitment of bone marrow precursors through expression of membrane-bound TRANCE","volume":"27","author":"Lean","year":"2000","journal-title":"Bone"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.biomaterials.2014.10.035","article-title":"Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators","volume":"37","author":"Vasconcelos","year":"2015","journal-title":"Biomaterials"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/S0140-6736(77)90592-X","article-title":"Bone-marrow transplantation in osteopetrosis","volume":"2","author":"Ballet","year":"1977","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1056\/NEJM198003273021301","article-title":"Successful bone-marrow transplantation for infantile malignant osteopetrosis","volume":"302","author":"Coccia","year":"1980","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/0002-9343(81)90839-1","article-title":"Marrow transplantation for juvenile osteopetrosis","volume":"70","author":"Sorell","year":"1981","journal-title":"Am. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/283669a0","article-title":"Osteoclasts derived from haematopoietic stem cells","volume":"283","author":"Ash","year":"1980","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14629","DOI":"10.1073\/pnas.0507637102","article-title":"Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero","volume":"102","author":"Frattini","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1126\/science.1105786","article-title":"Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells","volume":"190","author":"Walker","year":"1975","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41586-019-1105-7","article-title":"Developmental origin, functional maintenance and genetic rescue of osteoclasts","volume":"568","author":"Percin","year":"2019","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13619-024-00205-x","article-title":"Beyond resorption: Osteoclasts as drivers of bone formation","volume":"13","author":"Xiang","year":"2024","journal-title":"Cell Regen."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41556-019-0437-8","article-title":"Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair","volume":"22","author":"Yahara","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yahara, Y., Ma, X., Gracia, L., and Alman, B.A. (2021). Monocyte\/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.622035"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"dev199908","DOI":"10.1242\/dev.199908","article-title":"The origins and roles of osteoclasts in bone development, homeostasis and repair","volume":"149","author":"Yahara","year":"2022","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"868","DOI":"10.4049\/jimmunol.1900665","article-title":"Osteoclasts Derive Predominantly from Bone Marrow-Resident CX3CR1(+) Precursor Cells in Homeostasis, whereas Circulating CX3CR1(+) Cells Contribute to Osteoclast Development during Fracture Repair","volume":"204","author":"Novak","year":"2020","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e13714","DOI":"10.1111\/acel.13714","article-title":"A single short reprogramming early in life initiates and propagates an epigenetically related mechanism improving fitness and promoting an increased healthy lifespan","volume":"21","author":"Alle","year":"2022","journal-title":"Aging Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1089\/cell.2023.0072","article-title":"Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice","volume":"26","author":"Macip","year":"2024","journal-title":"Cell. Reprogram."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1089\/cell.2022.0153","article-title":"Early Life Reprogramming-Based Treatment Promotes Longevity","volume":"25","author":"Pessina","year":"2023","journal-title":"Cell. Reprogram."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1182\/bloodadvances.2021004552","article-title":"Novel population of human monocyte and osteoclast progenitors from pluripotent stem cells and peripheral blood","volume":"5","author":"Root","year":"2021","journal-title":"Blood Adv."},{"key":"ref_44","first-page":"113","article-title":"Generating human osteoclasts in vitro from bone marrow and peripheral blood","volume":"80","author":"Flanagan","year":"2003","journal-title":"Methods Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1359\/JBMR.051007","article-title":"Identification of multiple osteoclast precursor populations in murine bone marrow","volume":"21","author":"Jacquin","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1172\/JCI113916","article-title":"Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures","volume":"83","author":"Takahashi","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.stemcr.2015.04.012","article-title":"Identification of the Common Origins of Osteoclasts, Macrophages, and Dendritic Cells in Human Hematopoiesis","volume":"4","author":"Xiao","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3736","DOI":"10.1210\/endo.140.8.6880","article-title":"Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors","volume":"140","author":"Mbalaviele","year":"1999","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e82118","DOI":"10.7554\/eLife.82118","article-title":"Bone marrow Adipoq-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis, and bone mass","volume":"12","author":"Inoue","year":"2023","journal-title":"eLife"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41413-025-00405-4","article-title":"Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice","volume":"13","author":"Lu","year":"2025","journal-title":"Bone Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Qin, L., Lu, J., He, Q., Wang, H., Yao, L., Duffy, M., Guo, H., Braun, C., Lin, Y., and Zhou, Y. (2024). Bone marrow adipogenic lineage precursors are the major regulator of bone resorption in adult mice. Res Sq.","DOI":"10.21203\/rs.3.rs-4809633\/v1"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e82112","DOI":"10.7554\/eLife.82112","article-title":"Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone","volume":"12","author":"Zhong","year":"2023","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Flegar, D., Filipovic, M., Sucur, A., Markotic, A., Lukac, N., Sisl, D., Ikic Matijasevic, M., Jajic, Z., Kelava, T., and Katavic, V. (2021). Preventive CCL2\/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2(hi) Osteoclast Progenitors to the Affected Bone. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.767231"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/ijlh.12216","article-title":"CD14+ CD16+ monocytes rather than CD14+ CD51\/61+ monocytes are a potential cytological marker of circulating osteoclast precursors in multiple myeloma. A preliminary study","volume":"37","author":"Petitprez","year":"2015","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s00774-006-0725-9","article-title":"Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood","volume":"25","author":"Sorensen","year":"2007","journal-title":"J. Bone Miner. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13075-020-02308-7","article-title":"CD14(+)CD16(-) monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK","volume":"22","author":"Xue","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1158\/0008-5472.CAN-12-2202","article-title":"Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer","volume":"73","author":"Sawant","year":"2013","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1084\/jem.20101474","article-title":"Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo","volume":"207","author":"Ishii","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1002\/jbmr.1822","article-title":"Identification, characterization, and isolation of a common progenitor for osteoclasts, macrophages, and dendritic cells from murine bone marrow and periphery","volume":"28","author":"Lee","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1182\/blood.V80.7.1710.1710","article-title":"Identification and characterization of osteoclast progenitors by clonal analysis of hematopoietic cells","volume":"80","author":"Lee","year":"1992","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10006","DOI":"10.1073\/pnas.1207361109","article-title":"Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op\/op mice","volume":"109","author":"Nakamichi","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"605","DOI":"10.4049\/jimmunol.1201345","article-title":"Systemic circulation and bone recruitment of osteoclast precursors tracked by using fluorescent imaging techniques","volume":"190","author":"Kotani","year":"2013","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00223-012-9600-y","article-title":"Osteoclast fusion and fission","volume":"90","author":"Jansen","year":"2012","journal-title":"Calcif. Tissue Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1002\/jbmr.4314","article-title":"Neonatal Osteomacs and Bone Marrow Macrophages Differ in Phenotypic Marker Expression and Function","volume":"36","author":"Mohamad","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2015.12.017","article-title":"OsteoMacs: Key players around bone biomaterials","volume":"82","author":"Miron","year":"2016","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1073\/pnas.1315153111","article-title":"Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone","volume":"111","author":"Cho","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1002\/jbmr.4413","article-title":"Osteal macrophages support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model","volume":"36","author":"Batoon","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/jbmr.354","article-title":"Osteal macrophages promote in vivo intramembranous bone healing in a mouse tibial injury model","volume":"26","author":"Alexander","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_69","first-page":"4726529","article-title":"An Unusual Cause of Hypoxia: Ventricular Septal Defect, Pulmonary Artery Atresia, and Major Aortopulmonary Collaterals Diagnosed in the Adult Cardiac Catheterization Lab","volume":"2020","author":"Walton","year":"2020","journal-title":"Case Rep. Cardiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5659","DOI":"10.4049\/jimmunol.178.9.5659","article-title":"Lymphotoxin-independent expression of TNF-related activation-induced cytokine by stromal cells in cryptopatches, isolated lymphoid follicles, and Peyer\u2019s patches","volume":"178","author":"Taylor","year":"2007","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Sigl, V., Jones, L.P., and Penninger, J.M. (2016). RANKL\/RANK: From bone loss to the prevention of breast cancer. Open Biol., 6.","DOI":"10.1098\/rsob.160230"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"160230","DOI":"10.1042\/BSR20160150","article-title":"RANK-RANKL signalling in cancer","volume":"36","author":"Renema","year":"2016","journal-title":"Biosci Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S8756-3282(03)00097-8","article-title":"The surface antigen CD45R identifies a population of estrogen-regulated murine marrow cells that contain osteoclast precursors","volume":"32","author":"Katavic","year":"2003","journal-title":"Bone"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1172\/JCI60920","article-title":"Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function","volume":"122","author":"Charles","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/jre.12725","article-title":"Enhanced dual function of osteoclast precursors following calvarial Porphyromonas gingivalis infection","volume":"55","author":"Cai","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhou, J., Tang, Z., Gao, S., Li, C., Feng, Y., and Zhou, X. (2020). Tumor-Associated Macrophages: Recent Insights and Therapies. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00188"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/cei.12862","article-title":"Increased chemotaxis and activity of circulatory myeloid progenitor cells may contribute to enhanced osteoclastogenesis and bone loss in the C57BL\/6 mouse model of collagen-induced arthritis","volume":"186","author":"Flegar","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"17537","DOI":"10.1073\/pnas.1202870109","article-title":"Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes","volume":"109","author":"Kleinnijenhuis","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1251086","DOI":"10.1126\/science.1251086","article-title":"Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity","volume":"345","author":"Saeed","year":"2014","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Moerings, B.G.J., de Graaff, P., Furber, M., Witkamp, R.F., Debets, R., Mes, J.J., van Bergenhenegouwen, J., and Govers, C. (2021). Continuous Exposure to Non-Soluble beta-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.672796"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1084\/jem.190.12.1741","article-title":"Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors","volume":"190","author":"Arai","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1182\/blood.V96.13.4335","article-title":"An adherent condition is required for formation of multinuclear osteoclasts in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor kappa B ligand","volume":"96","author":"Miyamoto","year":"2000","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1083\/jcb.200806139","article-title":"Identification of cell cycle-arrested quiescent osteoclast precursors in vivo","volume":"184","author":"Mizoguchi","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1136\/annrheumdis-2018-213250","article-title":"Non-classical monocytes as mediators of tissue destruction in arthritis","volume":"77","author":"Puchner","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2302\/kjm.60.101","article-title":"Regulators of osteoclast differentiation and cell-cell fusion","volume":"60","author":"Miyamoto","year":"2011","journal-title":"Keio J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1182\/blood.V91.4.1272","article-title":"Isolation and characterization of murine clonogenic osteoclast progenitors by cell surface phenotype analysis","volume":"91","author":"Muguruma","year":"1998","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1182\/bloodadvances.2017008540","article-title":"Macrophages and osteoclasts stem from a bipotent progenitor downstream of a macrophage\/osteoclast\/dendritic cell progenitor","volume":"1","author":"Xiao","year":"2017","journal-title":"Blood Adv."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.coi.2010.06.007","article-title":"Stem cells and the aging hematopoietic system","volume":"22","author":"Beerman","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1677\/joe.0.1720673","article-title":"Gender- and age-related differences in osteoclast formation from circulating precursors","volume":"172","author":"Jevon","year":"2002","journal-title":"J. Endocrinol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e12923","DOI":"10.1111\/acel.12923","article-title":"Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice","volume":"18","author":"Kim","year":"2019","journal-title":"Aging Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S0047-6374(02)00071-4","article-title":"Osteoclastogenic potential of bone marrow cells increases with age in elderly women with fracture","volume":"123","author":"Koshihara","year":"2002","journal-title":"Mech. Ageing Dev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41413-020-0102-7","article-title":"Aging and menopause reprogram osteoclast precursors for aggressive bone resorption","volume":"8","author":"Moller","year":"2020","journal-title":"Bone Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Collins, F.L., Stone, M.D., Turton, J., McCabe, L.R., Wang, E.C.Y., and Williams, A.S. (2019). Oestrogen-deficiency induces bone loss by modulating CD14(+) monocyte and CD4(+) T cell DR3 expression and serum TL1A levels. BMC Musculoskelet. Disord., 20.","DOI":"10.1186\/s12891-019-2704-z"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e178977","DOI":"10.1172\/jci.insight.178977","article-title":"Cellular signatures in human blood track bone mineral density in postmenopausal women","volume":"9","author":"Kaneko","year":"2024","journal-title":"JCI Insight"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00198-008-0731-y","article-title":"Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo","volume":"20","author":"Clowes","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1080\/08820139.2018.1552360","article-title":"Myeloid-Derived Suppressor Cells at the Intersection of Inflammaging and Bone Fragility","volume":"47","author":"Kirkwood","year":"2018","journal-title":"Immunol. Investig."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5941","DOI":"10.1182\/blood-2010-08-300772","article-title":"Sphingosine kinase-1 and sphingosine 1-phosphate receptor 2 mediate Bcr-Abl1 stability and drug resistance by modulation of protein phosphatase 2A","volume":"117","author":"Salas","year":"2011","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e14298","DOI":"10.1111\/acel.14298","article-title":"Age-related increase of CD38 directs osteoclastogenic potential of monocytic myeloid-derived suppressor cells through mitochondrial dysfunction in male mice","volume":"23","author":"Thiyagarajan","year":"2024","journal-title":"Aging Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/8756-3282(94)90893-1","article-title":"Age-related bone loss in mice is associated with an increased osteoclast progenitor pool","volume":"15","author":"Perkins","year":"1994","journal-title":"Bone"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1359\/JBMR.050503","article-title":"Aging increases stromal\/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse","volume":"20","author":"Cao","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41586-021-03795-7","article-title":"Aged skeletal stem cells generate an inflammatory degenerative niche","volume":"597","author":"Ambrosi","year":"2021","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.bone.2005.09.018","article-title":"Osteoclastic activity begins early and increases over the course of bone healing","volume":"38","author":"Schell","year":"2006","journal-title":"Bone"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ydbio.2014.08.007","article-title":"In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts","volume":"394","author":"Takeyama","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"dev199803","DOI":"10.1242\/dev.199803","article-title":"Laser-mediated osteoblast ablation triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish","volume":"149","author":"Geurtzen","year":"2022","journal-title":"Development"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1038\/nm.3668","article-title":"PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis","volume":"20","author":"Xie","year":"2014","journal-title":"Nat. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/nyas.13629","article-title":"A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair","volume":"1415","author":"Walia","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e79966","DOI":"10.7554\/eLife.79966","article-title":"Osteoclast-mediated resorption primes the skeleton for successful integration during axolotl limb regeneration","volume":"11","author":"Tsai","year":"2022","journal-title":"Elife"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e20170601","DOI":"10.1590\/1678-7757-2017-0601","article-title":"Oral implant osseointegration model in C57Bl\/6 mice: Microtomographic, histological, histomorphometric and molecular characterization","volume":"26","author":"Biguetti","year":"2018","journal-title":"J. Appl. Oral Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1902\/jop.2000.71.2.287","article-title":"Tissue response to titanium implants in the rat maxilla: Ultrastructural and histochemical observations of the bone-titanium interface","volume":"71","author":"Futami","year":"2000","journal-title":"J. Periodontol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e486","DOI":"10.1111\/cid.12276","article-title":"Oxidized Titanium Implants Enhance Osseointegration via Mechanisms Involving RANK\/RANKL\/OPG Regulation","volume":"17","author":"Lenneras","year":"2015","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Makishi, S., Watanabe, T., Saito, K., and Ohshima, H. (2023). Effect of Hydroxyapatite\/beta-Tricalcium Phosphate on Osseointegration after Implantation into Mouse Maxilla. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043124"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1046\/j.0905-7161.2003.00960.x","article-title":"Tissue response to titanium implantation in the rat maxilla, with special reference to the effects of surface conditions on bone formation","volume":"14","author":"Shirakura","year":"2003","journal-title":"Clin. Oral. Implant. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1902\/jop.2006.050196","article-title":"Early cellular responses in cortical bone healing around unloaded titanium implants: An animal study","volume":"77","author":"Slaets","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1359\/jbmr.2002.17.2.192","article-title":"In vivo RANK signaling blockade using the receptor activator of NF-kappaB:Fc effectively prevents and ameliorates wear debris-induced osteolysis via osteoclast depletion without inhibiting osteogenesis","volume":"17","author":"Childs","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/gt.2010.64","article-title":"Cell-based osteoprotegerin therapy for debris-induced aseptic prosthetic loosening on a murine model","volume":"17","author":"Zhang","year":"2010","journal-title":"Gene Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/25785826.2021.1944547","article-title":"Arthritis-associated osteoclastogenic macrophages (AtoMs) participate in pathological bone erosion in rheumatoid arthritis","volume":"45","author":"Agemura","year":"2022","journal-title":"Immunol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1080\/25785826.2021.1913883","article-title":"Updating the pathophysiology of arthritic bone destruction: Identifying and visualizing pathological osteoclasts in pannus","volume":"44","author":"Hasegawa","year":"2021","journal-title":"Immunol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/s41590-019-0526-7","article-title":"Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1","volume":"20","author":"Hasegawa","year":"2019","journal-title":"Nat Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Filipovic, M., Flegar, D., Anicic, S., Sisl, D., Kelava, T., Kovacic, N., Sucur, A., and Grcevic, D. (2022). Transcriptome profiling of osteoclast subsets associated with arthritis: A pathogenic role of CCR2(hi) osteoclast progenitors. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.994035"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s13075-017-1337-6","article-title":"Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells","volume":"19","author":"Sucur","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"11846","DOI":"10.1074\/jbc.M512624200","article-title":"Tumor necrosis factor-alpha increases circulating osteoclast precursor numbers by promoting their proliferation and differentiation in the bone marrow through up-regulation of c-Fms expression","volume":"281","author":"Yao","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1038\/s41467-022-31475-1","article-title":"TGFbeta reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis","volume":"13","author":"Xia","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/JLB.1HI0620-230R","article-title":"Frontline Science: Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection","volume":"108","author":"Zhao","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1902\/jop.2005.76.11.1849","article-title":"Gingival crevicular fluid levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha in patients with chronic and aggressive periodontitis","volume":"76","author":"Kurtis","year":"2005","journal-title":"J. Periodontol."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"de Vries, T.J., El Bakkali, I., Kamradt, T., Schett, G., Jansen, I.D.C., and D\u2019Amelio, P. (2019). What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Various Inflammatory Diseases Associated with Bone Loss?. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00505"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Durstberger, G., Nguyen, P.Q., Hohensinner, V., Pietschmann, P., Rausch-Fan, X., and Andrukhov, O. (2021). Effect of Enamel Matrix Derivatives on Osteoclast Formation from PBMC of Periodontitis Patients and Healthy Individuals after Interaction with Activated Endothelial Cells. Medicina, 57.","DOI":"10.3390\/medicina57030269"},{"key":"ref_127","first-page":"e72","article-title":"Peripheral blood mononuclear phagocytes from patients with chronic periodontitis are primed for osteoclast formation","volume":"85","author":"Herrera","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/JPER.17-0306","article-title":"Platelet-rich fibrin\/biphasic calcium phosphate impairs osteoclast differentiation and promotes apoptosis by the intrinsic mitochondrial pathway in chronic periodontitis","volume":"90","author":"Kumar","year":"2019","journal-title":"J. Periodontol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/j.1600-051X.2008.01241.x","article-title":"Formation of osteoclast-like cells from peripheral blood of periodontitis patients occurs without supplementation of macrophage colony-stimulating factor","volume":"35","author":"Tjoa","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s12015-024-10711-9","article-title":"Trained innate immunity modulates osteoblast and osteoclast differentiation","volume":"20","author":"Rahmani","year":"2024","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41413-022-00206-z","article-title":"Specific inflammatory osteoclast precursors induced during chronic inflammation give rise to highly active osteoclasts associated with inflammatory bone loss","volume":"10","author":"Meirow","year":"2022","journal-title":"Bone Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.immuni.2020.10.011","article-title":"The Intersection of Epigenetics and Metabolism in Trained Immunity","volume":"54","author":"Fanucchi","year":"2021","journal-title":"Immunity"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.joca.2008.01.014","article-title":"Should subchondral bone turnover be targeted when treating osteoarthritis?","volume":"16","author":"Karsdal","year":"2008","journal-title":"Osteoarthr. Cartil."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.bone.2014.06.009","article-title":"Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression","volume":"66","author":"Siebelt","year":"2014","journal-title":"Bone"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e135446","DOI":"10.1172\/jci.insight.135446","article-title":"Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development","volume":"5","author":"Su","year":"2020","journal-title":"JCI Insight"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1093\/rheumatology\/keq188","article-title":"Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis","volume":"49","author":"Walsh","year":"2010","journal-title":"Rheumatology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"eabo7868","DOI":"10.1126\/sciadv.abo7868","article-title":"Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression","volume":"9","author":"Zhang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_138","doi-asserted-by":"crossref","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. Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T05:37:01Z","timestamp":1762234621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":138,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110619"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110619","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}