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Osteoclasts (OCs) are the active participants in the bone destruction of RA. Although with great advances, most current therapeutic strategies for RA have limited effects on bone destruction. Macrophage scavenger receptor A (SR-A) is a class of pattern recognition receptors (PRRs) involved in bone metabolism and OC differentiation. More recently, our study revealed the critical role of SR-A in RA diagnosis and pathogenesis. Here, we further demonstrated that serum SR-A levels were positively correlated with bone destruction in patients with RA. Anti-SR-A neutralizing antibodies significantly inhibited OC differentiation and bone absorption in vitro in patients with RA, but not in healthy individuals, dampening the expression of OC-specific genes such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and matrix metalloproteinase-9 (MMP-9). Similar results were also seen in collagen-induced arthritis (CIA) mice in vitro. Moreover, the anti-SR-A neutralizing antibody could further ameliorate osteoclastogenesis in vivo and ex vivo in CIA mice, accompanied by decreased serum levels of C-terminal telopeptide and IL-6, exhibiting potential protective effects. These results suggest that blockade of SR-A using anti-SR-A neutralizing antibodies might provide a promising therapeutic strategy for bone destruction in the RA.<\/jats:p>","DOI":"10.1093\/cei\/uxac010","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T19:27:08Z","timestamp":1644348428000},"page":"297-306","source":"Crossref","is-referenced-by-count":9,"title":["SR-A neutralizing antibody: potential drug candidate for ameliorating osteoclastogenesis in rheumatoid arthritis"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1368-4264","authenticated-orcid":false,"given":"Yang","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7031-3526","authenticated-orcid":false,"given":"Mingxin","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yundi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanguo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"},{"name":"Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanlei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China"},{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"2022051714132307500_CIT0001","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis.","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"2022051714132307500_CIT0002","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41413-018-0016-9","article-title":"Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.","volume":"6","author":"Guo","year":"2018","journal-title":"Bone Res"},{"key":"2022051714132307500_CIT0003","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/art.1780140605","article-title":"Methods of scoring the progression of 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