Unloading of occlusal force aggravates alveolar bone loss in periodontitis

Periodontitis (PD), a chronic infectious inflammatory disease initiated by bacteria, is associated with several local contributing factors including occlusal trauma. Previous studies have found that the traumatic occlusal force could aggravate alveolar bone loss during PD. However, the effect of reduced occlusal force during PD remains unclear. This study aimed to explore the effect of occlusal force unloading on PD onset and progression and its underlying mechanism as an effort to provide restoration suggestions for PD patients with dentition defect in clinic. This study might also propose occlusal force unloading could be a new local contributing factor for PD. C57BL/6 mice were used to establish a PD model by the ligation around the mandibular left first molar (PD group) and an unloading experiment model by extraction of their left maxillary first molar (PD+EX group). Micro-CT scanning and H&E staining results consistently showed that PD+EX group experienced the most severe alveolar bone resorption as compared with PD group and control group. Further RNA-sequencing analysis suggested that occlusal force unloading significantly enhance both osteoclastic resorption and M1 macrophages polarization, while inhibiting osteoblastic activity. Similar findings were observed in THP-1 derived macrophages in vitro. Collectively, our study demonstrated that unloading of occlusal force aggravates bone resorption by mediating M1 macrophages polarization during PD, suggesting a previously unknown contributing local factor for periodontitis, and providing a novel insight for dentists to restore missing teeth as an effort to maintain remaining dentition.