25dkou195 10.3205/25dkou195 urn:nbn:de:0183-25dkou1956 Meeting Abstract Zhu Zhu Mengbo M

Department of Orthopedics and Trauma Surgery, University Hospital Bonn, Bonn, Deutschland

author Xu Xu Mingwei M

Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, China

author Bertheloot Bertheloot Damien D

Department of Orthopedics and Trauma Surgery, University Hospital Bonn, Bonn, Deutschland

author Brom Brom Victoria V

Department of Orthopedics and Trauma Surgery, University Hospital Bonn, Bonn, Deutschland

author Sieberath Sieberath Alexander A

Department of Experimental Surgery, Centre for Clinical Research, Ruhr-Universität Bochum, Bochum, Deutschland

author Salber Salber Jochen J

Department of Experimental Surgery, Centre for Clinical Research, Ruhr-Universität Bochum, Bochum, Deutschland Department of Surgery, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland

author Wang Wang Shaowei S

Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, China

author Schildberg Schildberg Frank Alexander FA

Department of Orthopedics and Trauma Surgery, University Hospital Bonn, Bonn, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20251031 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). M0634 195 Deutsche Gesellschaft für Orthopädie und Unfallchirurgie Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie Deutsche Gesellschaft für Unfallchirurgie Berufsverband für Orthopädie und Unfallchirurgie Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2025) Posterpreise experimentell Berlin 20251028 20251031 AB28-4654 TextObjectives and questions: Macrophage polarization influences osteoclast differentiation, a process regulated by the JAK-STAT3 pathway. CDK4 inhibits this pathway by preventing STAT3 activation. We identified Arcyriaflavin A (ArcyA), an indole-based compound, as a natural CDK4 inhibitor and investigated its effects on osteoclast differentiation, aiming to explore its therapeutic potential for osteoporosis.Material and methods: Bone marrow-derived macrophages (BMMs) from C57 mice were stimulated with M-CSF and RANKL to induce osteoclast differentiation. ArcyA was administered, and TRAP staining was performed to assess osteoclast formation. qPCR and Western blot analyses were used to evaluate key osteoclast-related genes and proteins (Nfatc1, Ctsk, ATP6v0d2). Osteoclast function was examined using a bone resorption assay on an apatite-coated plate.To further validate the effects of ArcyA, osteoclasts derived from human peripheral blood were used. Additionally, an OVX-induced osteoporosis mouse model was treated with ArcyA, followed by micro-CT analysis to assess bone loss.Results: ArcyA significantly inhibited osteoclast differentiation and function. TRAP staining showed fewer multinucleated osteoclasts in the treatment group. qPCR and Western blot analyses confirmed downregulation of osteoclastogenesis markers (Nfatc1, c-Fos, Tnfrs11a) and resorption-related genes (Mmp9, Ctsk, Integrin β3). Osteoclast fusion genes (Dcstamp, ATP6v0d2) were also suppressed.Bone resorption assays revealed reduced osteoclastic activity in ArcyA-treated cells. In vivo, ArcyA administration significantly alleviated osteoporosis symptoms in OVX mice. In human primary osteoclasts, ArcyA exhibited inhibitory effects even at low concentrations (0.1 μM/L).Discussion and conclusions: This study highlights CDK4 inhibition as a novel strategy for osteoporosis treatment by suppressing osteoclastogenesis. ArcyA, as a CDK4 inhibitor, effectively reduced osteoclast differentiation and bone resorption, supporting its potential as an immunotherapeutic agent. Further studies will focus on the metabolic impact of CDK4 inhibition and its role in osteoclast function. 0 0 0 0