Autotaxin/Lysophosphatidic Acid Axis Promotes Periodontitis by Modulating Macrophage Osteoclastogenesis and Inflammation
Enyan Liu, Jiacheng Ding, Yiting Jiang, Yining Zhou, Lina Xu, Zhiyan He, Wei Zhou, Zhongchen SongABSTRACT
Aim
To investigate the mechanism of the autotaxin/lysophosphatidic acid (ATX/LPA) axis in regulating osteoclastogenesis and inflammation in periodontitis.
Materials and Methods
The expression levels and clinical relevance of the ATX/LPA axis were studied by collecting clinical samples including gingiva and gingival crevicular fluid from periodontitis patients and healthy subjects. Subsequently, macrophage Atx knockout (CKO) mice and bone marrow–derived macrophages (BMDMs) were generated to investigate the role of the ATX/LPA axis in modulating osteoclastogenesis and inflammation during periodontitis development. Finally, the ATX inhibitor PF8380 was used to explore a promising therapeutic strategy for controlling periodontitis. Histomorphological, molecular and cytological analyses were performed using RNA sequencing, real‐time polymerase chain reaction, immunofluorescence, immunohistochemistry, enzyme‐linked immunosorbent assay, micro‐computed tomography, haematoxylin and eosin staining, tartrate‐resistant acid phosphatase staining, actin filament staining, pit resorption assay and flow cytometry.
Results
The expression of the ATX/LPA axis was more enhanced in the periodontitis group than that in the health group and was positively correlated with the severity of periodontitis. Subsequently, CKO mice showed milder inflammation and less bone resorption than wild‐type (WT) mice of periodontitis. Following
Conclusion
The ATX/LPA axis plays a significant regulatory role in osteoclastogenesis and osteoclast activity and may enable selective control of bone loss and inflammation in periodontitis. Therefore, targeting ATX inhibition may represent a novel therapeutic strategy for preventing alveolar bone resorption and periodontal inflammation in patients with periodontitis.