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In terms of the action mechanism, FA-LDH modulated the nucleocytoplasmic transport of the small mothers against decapentaplegic 5 (Smad5) protein by adjusting the pH within the immune microenvironment. Subsequently, relying on the interaction between phospho-Smad5 (pSmad5) and p65, the nuclear factor kappa B signaling pathway was down-regulated through inhibiting nuclear transport of p65. Additionally, FA-LDH exhibited excellent targeting capability toward M1 macrophages and strong accumulation capacity in inflamed joints. In\u00a0vivo experiment showed that FA-LDH could relieve swelling of limbs, reduce the infiltration of inflammatory cells, and protect joint cartilage and subchondral bone structure in collagen-induced arthritis mice. In summary, this work introduces a strategy for utilizing bioactive FA-LDH in the treatment of RA, highlighting the potential of FA-LDH to alleviate inflammation and reshape the immune microenvironment through the pSmad5\/p65 axis.<\/jats:p>","DOI":"10.34133\/bmr.0176","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T14:31:45Z","timestamp":1743172305000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":3,"title":["Layered Double Hydroxide Reshapes the Immune Microenvironment of Rheumatoid Arthritis through Small Mothers against Decapentaplegic 5"],"prefix":"10.34133","volume":"29","author":[{"given":"Dengju","family":"Li","sequence":"first","affiliation":[{"name":"Department of Joint Surgery, \rShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, \rShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic, \rShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, Shandong Provincial Hospital, \rShandong University, Jinan, Shandong 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, Shandong Provincial Hospital, \rShandong University, Jinan, Shandong 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, Shandong Provincial Hospital, \rShandong University, Jinan, Shandong 250012, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, \rShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China."},{"name":"Department of Joint Surgery, Shandong Provincial Hospital, \rShandong University, Jinan, Shandong 250012, China."},{"name":"Orthopaedic Research Laboratory, Medical Science and Technology Innovation Center, \rShandong First Medical University &amp; 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