gms | German Medical Science

Objectives: Osteoporosis is one of the most common risk factors for fractures in the elderly population. It is a disease that causes a decrease in bone density and an alteration in the microarchitecture of the bone tissue, rending the bones weakened and vulnerable against trauma. Previous studies have revealed that Programmed Death Ligand 1 (PDL1, gene name Cd274), a type 1 transmembrane protein, might play a role in osteoporosis and suggested that it might have an inhibitory effect on the disease, hence helping to maintain a better bone density. In this study, we evaluate the bone phenotype of Cd274 knock-out (KO) mice in comparison of wild type mice.

Methods: From C57BL/6J control and Cd274 KO mice (males and females, aged between 26–34 weeks for both groups) bilateral femora, tibiae, humeri and lumbar vertebrae (L5-L6) were collected. Micro CT scans were used to evaluate the density and the morphometry in diaphysis and epiphysis of femora and tibiae as well as in lumbar vertebrae, while a biomechanical 3-points bending test was used to determine the ability to resist external stress in femora. Furthermore, an ashing test was used to analyse the organic and anorganic bone composition in femora. The statistical significance was set to p<0.05 and the unpaired T-Test was used to analyse the data.

Results and conclusion: Micro CT evaluation showed that femoral cortical volume (p<0.001), femoral (p=0.011) and tibial (p=0.016) cortical wall thickness, L5 trabecular volume (p<0.009), L5 (p<0.001) and L6 (p=0.033) bone volume/trabecular volume were higher in Cd274 KO group compared to control group. In addition, trabecular spacing in femoral (p=0.037) and tibial (p=0.0434) epiphysis were lower in Cd274 KO group in comparison to control group. Furthermore, biomechanical testing showed that yield load (p<0.001), stiffness (p<0.001) and maximal force endured before breaking (p=0.002) were higher in Cd274 KO group than in control. Additionally, ashing analysis revealed that the anorganic content (%) of femora (p=0.038) was higher in Cd274 KO group when compared to control group.

The results of this study show that the bone density in Cd274 KO mice seemed to be higher than in wild type mice, and that the Cd274 KO mice bones were richer in anorganic content. Moreover, the bones of Cd274 KO mice showed higher resistance to external force and thus to fractures than wild mice bones. Hence, we would conclude that PDL1 may play a role in the loss of cortical and trabecular bone, leading to a lower bone density and quality, and therefore PDL1 might contribute to promoting osteoporosis, as opposite to what was previously suggested.