The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections
Abstract Periprosthetic joint infection (PJI) is a critical complication following arthroplasty, leading to increased prosthesis failure rates post-treatment. This study explores the role of PD-1/PD-L1 signaling in osteoclastogenesis associated with PJI. Peripheral blood, bone, and bone marrow of 65...
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Nature Portfolio
2025-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08143-3 |
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| author | Yi Ren Denise Jahn Stefanie Donner Clemens Gwinner Weijie Du Dimitrios L. Wagner Serafeim Tsitsilonis Carsten Perka Georg Duda Arne Kienzle |
| author_facet | Yi Ren Denise Jahn Stefanie Donner Clemens Gwinner Weijie Du Dimitrios L. Wagner Serafeim Tsitsilonis Carsten Perka Georg Duda Arne Kienzle |
| author_sort | Yi Ren |
| collection | DOAJ |
| description | Abstract Periprosthetic joint infection (PJI) is a critical complication following arthroplasty, leading to increased prosthesis failure rates post-treatment. This study explores the role of PD-1/PD-L1 signaling in osteoclastogenesis associated with PJI. Peripheral blood, bone, and bone marrow of 65 patients (20 primary osteoarthritis, 21 PJI septic explantation, 24 PJI prosthesis reimplantation) were analyzed for their bone microstructure and cell composition. Immunocytochemistry, RT-qPCR, flow cytometry, bone resorption assay, ELISA, and RNA sequencing were performed to investigate the effects of PD-1 stimulation and blockade on osteoclast formation. PD-1 positive monocytes and sPD-L1 levels were elevated in PJI. Stimulation with PD-L1 enhanced osteoclastogenesis, while PD-1 inhibitor nivolumab reversed these effects. Impact of PD-1 and nivolumab was significantly more pronounced in PJI compared to the control. Our study suggests PD-1/PD-L1 signaling plays a significant role in PJI-related osteoclastogenesis. These findings highlight the potential of PD-1 inhibitors as a novel approach to manage this challenging clinical condition. |
| format | Article |
| id | doaj-art-8459edb8f2df4eeea3528e62120ed55a |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-8459edb8f2df4eeea3528e62120ed55a2025-08-20T02:34:19ZengNature PortfolioCommunications Biology2399-36422025-05-018111110.1038/s42003-025-08143-3The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infectionsYi Ren0Denise Jahn1Stefanie Donner2Clemens Gwinner3Weijie Du4Dimitrios L. Wagner5Serafeim Tsitsilonis6Carsten Perka7Georg Duda8Arne Kienzle9Center for Musculoskeletal Surgery, Clinic for Orthopedics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthCenter for Musculoskeletal Surgery, Clinic for Orthopedics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthCenter for Musculoskeletal Surgery, Clinic for Orthopedics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthBIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charité - Universitätsmedizin BerlinBIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health (BIH) at Charité - Universitätsmedizin BerlinCenter for Musculoskeletal Surgery, Clinic for Orthopedics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthCenter for Musculoskeletal Surgery, Clinic for Orthopedics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthJulius Wolff Institute and Center for Musculoskeletal Surgery, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthCenter for Musculoskeletal Surgery, Clinic for Orthopedics, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthAbstract Periprosthetic joint infection (PJI) is a critical complication following arthroplasty, leading to increased prosthesis failure rates post-treatment. This study explores the role of PD-1/PD-L1 signaling in osteoclastogenesis associated with PJI. Peripheral blood, bone, and bone marrow of 65 patients (20 primary osteoarthritis, 21 PJI septic explantation, 24 PJI prosthesis reimplantation) were analyzed for their bone microstructure and cell composition. Immunocytochemistry, RT-qPCR, flow cytometry, bone resorption assay, ELISA, and RNA sequencing were performed to investigate the effects of PD-1 stimulation and blockade on osteoclast formation. PD-1 positive monocytes and sPD-L1 levels were elevated in PJI. Stimulation with PD-L1 enhanced osteoclastogenesis, while PD-1 inhibitor nivolumab reversed these effects. Impact of PD-1 and nivolumab was significantly more pronounced in PJI compared to the control. Our study suggests PD-1/PD-L1 signaling plays a significant role in PJI-related osteoclastogenesis. These findings highlight the potential of PD-1 inhibitors as a novel approach to manage this challenging clinical condition.https://doi.org/10.1038/s42003-025-08143-3 |
| spellingShingle | Yi Ren Denise Jahn Stefanie Donner Clemens Gwinner Weijie Du Dimitrios L. Wagner Serafeim Tsitsilonis Carsten Perka Georg Duda Arne Kienzle The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections Communications Biology |
| title | The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections |
| title_full | The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections |
| title_fullStr | The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections |
| title_full_unstemmed | The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections |
| title_short | The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections |
| title_sort | role of pd 1 pd l1 in overshooting osteoclastogenesis in periprosthetic joint infections |
| url | https://doi.org/10.1038/s42003-025-08143-3 |
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