26rhk034 10.3205/26rhk034 urn:nbn:de:0183-26rhk0348 Meeting Abstract Khodaverdi Khodaverdi Negar N

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Arnold Arnold Mona M

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Frommer Frommer Klaus W. KW

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Klemm Klemm Philipp P

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Hermann Hermann Walter W

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Tarner Tarner Ingo I

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Biehl Biehl Christoph C

University Hospital of Giessen and Marburg, Department of Trauma, Hand and Reconstructive Surgery, Giessen, Deutschland

author Rickert Rickert Markus M

University Hospital of Giessen and Marburg, Department of Orthopaedics and Orthopaedic Surgery, Giessen, Deutschland

author Rehart Rehart Stefan S

Agaplesion Markus Hospital, Department of Orthopaedics and Trauma Surgery, Frankfurt, Deutschland

author Müller-Ladner Müller-Ladner Ulf U

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author Neumann Neumann Elena E

Justus-Liebig-University, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20260909 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0656 034 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie Gesellschaft für Kinder- und Jugendrheumatologie 54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2026 Experimentelle & Translationale Rheumatologie Leipzig 20260909 20260912 ET.07 TextIntroduction: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which activated synovial fibroblasts (SF) drive joint erosion. In these cells, integrin expression is increased, enhancing adhesion, migration, and proliferation. Integrin activation is mediated by focal-adhesion proteins such as kindlins and talin-1, yet their precise role in pro-inflammatory RASF activation remains unclear. This study was conducted to identify the significance of kindlins and talin-1 in RASF in vitro under pro-inflammatory stimulation and in vivo in the SCID mouse model.Methods: RASF were subjected to a single IL-1β dose (10 ng/mL) for 6, 17, 24 or 48 h, or to a repeated 0.05 ng/mL IL-1β pulse every 24 h (16 h stimulation, 8 h recovery) over 3 days, then collected for RNA sequencing. Expression of kindlins-1/2/3 and talin-1 was quantified bei qPCR and immunocytochemistry, while cytokine secretion assessed the inflammatory response by ELISA. In vivo, RASF together with human cartilage were implanted into SCID mice. Three mice at 30, 40, and 45 days after the implantation were randomly selected to assess expression of kindlins and talin-1 as well as cartilage invasion.Results: Kindlin-2 and talin-1 were highly expressed near vessels and in the synovial lining, sublining, and cartilage-invasion areas of SCID-mouse implants at all time points. After 17 hours, IL-1β stimulation of RASF resulted in a significant short term down-regulation of kindlin-2 (-4.1-fold, p=0.0456) compared to controls. After 48 h, the expression levels returned to baseline. Talin-1 showed the highest mRNA levels (663.1±186.2) followed by kindlin-2 (88.9±23.2), -1 (2.15±2.06) and -3 showing the lowest expression (0.12±0.08). Kindlin-1 expression was significantly increased after 6 h (2.9-fold, p=0.0178) but reduced after 17 h (-1.5-fold, p<0.0001), 24 h (-0.7-fold, p=0.0004) and 48h (-1.2-fold, p<0.0001). These transcriptional changes observed by RNAseq and qPCR were corroborated by immunocytochemistry of RASF and in RA tissue. RNAseq with repeated inflammatory flares showed that kindlin and talin expression remained altered in contrast to reduced inflammatory induction observed after repetitive IL-1β stimulation.Conclusion: Kindlin-2 and talin-1 are expressed in RASF and RA synovial tissue, including RASF actively invading cartilage in SCID-mouse implants. Inflammatory cues alter the temporal expression of these proteins, activation of RASF likely enhanced their adhesion and migration behaviour. 0 0 0 0