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The orchestration of complement component activation is closely linked to bone remodeling and the maintenance of skeletal homeostasis. C3a and C5a are notably influential in modulating the differentiation and activity of bone remodeling cells\u2014including osteoclasts, osteoblasts, and osteocytes. Elevated expression or excessive activation of complement components is recognized as a major contributor to bone injury in a variety of inflammatory skeletal disorders. The therapeutic role of complement factors has been evaluated in several models of skeletal diseases. A comprehensive understanding of the complement system in bone remodeling and its therapeutic implications may help in designing innovative strategies to prevent bone degradation and disorders. This review discusses the relationship between the complement system, bone homeostasis, and bone-associated inflammatory diseases. Furthermore, we examine the complement system's potential and its limitations in complement-targeted therapies.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag109","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:37:11Z","timestamp":1785843431000},"source":"Crossref","is-referenced-by-count":0,"title":["Complement system in bone inflammation and autoimmunity"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-5142","authenticated-orcid":false,"given":"Adrita","family":"Guha","sequence":"first","affiliation":[{"name":"BRIC-National Centre for Cell Science (NCCS) , Ganeshkhind, Pune, Maharashtra 411007 ,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind, Pune, MH 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praneet","family":"Wahi","sequence":"additional","affiliation":[{"name":"BRIC-National Centre for Cell Science (NCCS) , Ganeshkhind, Pune, Maharashtra 411007 ,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind, Pune, MH 411007 ,","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":"BRIC-National Centre for Cell Science (NCCS) , Ganeshkhind, Pune, Maharashtra 411007 ,","place":["India"]},{"name":"Department of Biotechnology, Savitribai Phule Pune University , Ganeshkhind, Pune, MH 411007 ,","place":["India"]},{"name":"Regional Centre for Biotechnology , Faridabad, HR 121001 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026082511561470100_qiag109-B1","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1056\/NEJM200104053441406","article-title":"Complement. 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