CD274 Knockout Promotes Bone Formation and Reduces Osteoclast Activity
In brief
Deleting Cd274 increased bone mass and strength in mature mice
At 26 weeks, mice lacking Cd274 had thicker, more voluminous cortical bone, less trabecular space, and stronger femurs than control mice; they also had fewer osteoclasts in some bones. Because these were healthy mice with a lifelong gene knockout, the findings do not show that blocking PD-L1 treats osteoporosis, and dedicated disease-model studies are still needed.
- Journal
- Calcified tissue international (Q1)
- Published
- 20 October 2026
- Study design
- Unclassified
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Hadi El Assaad, Marina Komrakova, Stefan Lienenklaus, Sebastian Decker, Claudia Neunaber, Katrin Bundkirchen
- PMID
- 42900228
- DOI
- 10.1007/s00223-026-01627-2
Why clinicians should know about it
- Picked for Histology (paper of the day, 23 October 2026): Healthy-mouse bone microarchitecture, histology, and cell counts
Abstract
Osteoporosis is a systemic disease characterized by decreased bone density, and deterioration in the micro-architectural remodelling of bone tissue, leading to an increased susceptibility to bone fractures. One molecule implicated in bone metabolism is Programmed Death Ligand 1 (PD-L1), a pharmacologically targetable immune-checkpoint molecule encoded by the gene Cd274. The aim of this study was to investigate the bone phenotype of Cd274 knockout (KO) mice at 26 weeks of age compared to C57BL/6J control wildtype mice on radiological, histological and biomechanical level. The cortical wall thickness and cortical volume increased, and the trabecular space decreased significantly in both femur and tibia of Cd274 KO mice. Moreover, there was a significant increase in BV/TV and trabecular volume of lumbar vertebrae of Cd274 KO mice. Yield load, stiffness, anorganic amount increased and organic amount decreased significantly in femoral bones of Cd274 KO mice. Additionally, there was a significantly higher number of osteocytes and lower number of osteoclasts in both humerus and lumbar vertebra of Cd274 KO mice. The findings demonstrate that constitutive knockout of Cd274 was associated with significantly increased bone mass and strength. These results-obtained in healthy, skeletally mature constitutive knockout mice-indicate an improved bone phenotype in the absence of Cd274 and thus contrast with previous studies that associate disruption of the PD-1/PD-L1 axis, including immune checkpoint inhibitor therapy, with bone loss and increased fracture risk. Further studies, particularly in dedicated osteoporosis models, are required to elucidate the influence of CD274 on bone metabolism before translational conclusions can be drawn.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.