ArticleFrontiers in immunology2022
The Programmed Death-1 Pathway Counter-Regulates Inflammation-Induced Osteoclast Activity in Clinical and Experimental Settings.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 25 citations in OpenAlex.
- Cytokine-induced PD-L1 and PD-L2 expression is preserved but reverse signalling is altered in rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- Research progress of drug-induced osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Immune Checkpoint Inhibitors and Bone Health: Mechanisms, Clinical Implications, and Emerging Perspectives on Bone Fragility.Current osteoporosis reports · 2026Review
- Bone Adverse Events in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy: A Comprehensive Review of the Literature from the Clinical Action Group of the European Calcified Tissue Society.Calcified tissue international · 2026Review
- Severe Hypercalcemia Following Pembrolizumab Therapy: A Case Report and A Literature ReviewEndocrine, metabolic & immune disorders drug targets · 2026Review
- Article
- Programmed cell death protein 1 (PD-1) blockade regulates skeletal remodeling in a sex- and age-dependent manner.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Association of Soluble Immune Checkpoint Molecules PD1 and 4-1BB With CTLA-4Ig Treatment Response in Early Rheumatoid Arthritis.ACR open rheumatology · 2025Article
- The role of PD-1/PD-L1 in overshooting osteoclastogenesis in periprosthetic joint infections.Communications biology · 2025Article
- RNA interference-mediated osteoprotegerin silencing increases the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio and promotes osteoclastogenesis.World journal of stem cells · 2025Article
- The regulatory effects of PD-1/PD-L1 inhibitors on bone metabolism: opportunities and challenges in osteoporosis management.Frontiers in immunology · 2025Review
- Incidence of fractures in patients with solid cancers treated with immune checkpoint inhibitors: a systematic review and meta-analysis of randomised controlled trials.BMJ oncology · 2025Article
- Correlation between PD-1/PD-L1 and RANKL/OPG in chronic apical periodontitis model of Sprague-Dawley rats.Odontology · 2024Article
- Immune-related osteoblastic bone alterations mimicking bone metastasis in a small-cell lung cancer patient treated with durvalumab: a case report.Translational lung cancer research · 2024Article
- Immune checkpoint inhibitors in bone metastasis: Clinical challenges, toxicities, and mechanisms.Journal of bone oncology · 2023Review
- Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes.Biomedicines · 2023Article
- Galectin-3 interacts with PD-1 and counteracts the PD-1 pathway-driven regulation of T cell and osteoclast activity in Rheumatoid Arthritis.Scandinavian journal of immunology · 2023Article
- The effect of combining PD-1 agonist and low-dose Interleukin-2 on treating systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Agonistic and antagonistic targeting of immune checkpoint molecules differentially regulate osteoclastogenesis.Frontiers in immunology · 2023Article
- Co-Inhibitory Molecules - Their Role in Health and Autoimmunity; Highlighted by Immune Related Adverse Events.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Objective: The programmed death-1 (PD-1) pathway is essential for maintaining self-tolerance and plays an important role in autoimmunity, including rheumatoid arthritis (RA). Here, we investigated how membrane-bound and soluble (s)PD-1 influence bone homeostasis during chronic inflammation, exemplified in RA. Methods: Bone mineral density and bone microstructure were examined in PD-1 and PD-L1 knockout (KO) mice and compared with wild-type (WT) mice. Receptor activator of nuclear factor kappa-B ligand (RANKL) was measured in serum, and the expression examined on activated bone marrow cells. Osteoclast formation was examined in cells from murine spleen and bone marrow and from human synovial fluid cells. sPD-1 was measured in chronic and early (e)RA patients and correlated to markers of disease activity and radiographic scores. Results: PD-1 and PD-L1 KO mice showed signs of osteoporosis. This was supported by a significantly reduced trabecular bone volume fraction and deteriorated microstructure, as well as increased osteoclast formation and an increased RANKL/OPG ratio. The recombinant form of sPD-1 decreased osteoclast formation Conclusion: The PD-1 pathway is closely associated with bone homeostasis, and lacking members of this pathway causes a deteriorated bone structure. The immunological balance in the microenvironment determines how the PD-1 pathway regulates osteoclast formation. In eRA patients, sPD-1 may serve as a biomarker, reflecting residual but clinically silent disease activity and radiographic progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.