{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:13:03Z","timestamp":1787728383857,"version":"build-2784847793"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Swarna Jayanti Fellowship","award":["DST\/SJF\/LSA-01\/2017-2018"],"award-info":[{"award-number":["DST\/SJF\/LSA-01\/2017-2018"]}]},{"DOI":"10.13039\/100021014","name":"Department of Science and Technology","doi-asserted-by":"publisher","award":["HRD-16012\/5\/2024-HRD-DBT"],"award-info":[{"award-number":["HRD-16012\/5\/2024-HRD-DBT"]}],"id":[{"id":"10.13039\/100021014","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Biotechnology, Ministry of Science and Technology, Government of India"},{"name":"Anusandhan National Research Foundation","award":["CRG\/2023\/001054"],"award-info":[{"award-number":["CRG\/2023\/001054"]}]},{"name":"Ministry of Science and Technology, Government of India"},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The pathomechanistic role of the complement system is well recognized in various pathological conditions affecting bone tissues and the bone microenvironment, including rheumatoid arthritis, osteoarthritis, bone fractures, and periodontitis. The homeostasis of the bone is maintained by continuous remodeling, in which bone-resorbing or demineralizing osteoclast cells remove bone calcification, and osteoblast cells deposit new bone matrix. Major complement protein C3 is reported to control endochondral ossification, cartilage-to-bone transition, and longitudinal bone growth. The role of the complement protein C3 in differentiating multinucleated osteoclast cells (bone-resorbing cells) from osteoclast precursor cells (OCPs) and its contribution to long bone microarchitecture and strength are unclear. We demonstrated that C3 promotes the differentiation of osteoclasts and the formation of multinucleated osteoclasts from bone marrow\u2013derived OCPs. C3\u2212\/\u2212 mice OCPs had reduced osteoclast-associated gene expression of TRAP (tartrate-resistant acid phosphatase), cathepsin K, calcitonin receptor, and RANK (receptor activator of nuclear factor \u03baB) molecules compared with osteoclasts derived from wild-type (WT) OCPs. C3\u2212\/\u2212 mice had significantly increased bone mineral density and other bone parameters of the femur compared with WT mice. Furthermore, compared with WT mice, C3\u2212\/\u2212 mice were protected from ovariectomy-induced osteoporosis, characterized by significantly increased Foxp3+CD4+ T cells in the spleen and interleukin-10\u2013producing B cells in both the spleen and the bone marrow. Intriguingly, C3 knockout mice exhibit reduced differentiation of functional osteoclast cells, which promotes a strong bone microarchitecture, suggesting that complement pathways may be explored as a therapeutic target in bone inflammatory diseases.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf180","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T05:09:58Z","timestamp":1755925798000},"page":"3069-3082","source":"Crossref","is-referenced-by-count":6,"title":["Complement C3 deficiency inhibits osteoclast differentiation and prevents ovariectomy-induced osteoporosis"],"prefix":"10.1093","volume":"214","author":[{"given":"Adrita","family":"Guha","sequence":"first","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpita","family":"Prasad","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Ashokkumar","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0391-6084","authenticated-orcid":false,"given":"Pradipta","family":"Pal","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Sahu","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Regional Centre for Biotechnology, NCR Biotech Science Cluster , Faridabad, Haryana 121001,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan R","family":"Wani","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Regional Centre for Biotechnology, NCR Biotech Science Cluster , Faridabad, Haryana 121001,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3799-3603","authenticated-orcid":false,"given":"Girdhari","family":"Lal","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Biotechnology Research and Innovation Council , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind , Pune, Maharashtra 411007,","place":["India"]},{"name":"Regional Centre for Biotechnology, NCR Biotech Science Cluster , Faridabad, Haryana 121001,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"2025112603024580700_vkaf180-B1","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1210\/jc.2008-1878","article-title":"Bone mineral density in estrogen-deficient young women","volume":"94","author":"Popat","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"2025112603024580700_vkaf180-B2","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1093\/humrep\/deae037","article-title":"Bone health in women with premature ovarian insufficiency\/early menopause: a 23-year longitudinal analysis","volume":"39","author":"Jones","year":"2024","journal-title":"Hum 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