TNF antagonist prevents inhibitory effects of LPS on bone formation

Objectives: The release of tumor necrosis factor (TNF)-α from macrophages upon the aqdisease. Cavity Induced Allosteric Modification (CIAM) compound is newly chemical antagonist which binds TNF recepter. The CIAM compound prevents TNF-α induced signal transduction in the cell. In this study, we examined whether the CIAM compound can prevent the inhibitory effcts of LPS on bone formation or not, using the tooth extraction model. Methods: Forty-two 10-week-old males mice (WT: C57BL/6J) were used in this study. Mice were devided into 6 groups (n=7), such as PBS/Vehicle, PBS/Low-dose CIAM, PBS/High-dose CIAM, LPS/Vehicle, LPS/Low-dose CIAM, and LPS/High-dose CIAM . First, the left mandibular incisor was cut at the gingival margin. Four days after tooth cutting, the left incisor was extracted. LPS (10 mg/kg) or PBS was injected subcutaneously into the calvariae on the day of tooth cutting. Intraperitoneal injections of either the Low-dose CIAM compound (2 mg/kg/d), the High-dose CIAM compound (4 mg/kg/d) or vehicle (10% DMSO) were performed in each experimental group once a day for 7 days. For fluorescent labeling, calcein and demeclocycline injected subcutaneously. The mice were killed on day 21 after tooth extraction. Bone mineral density (BMD) of the tooth socket was measured by pQCT. Results: The BMD in the tooth socket was significantly decreased by LPS/Vehicle group compared with the PBS/Vehicle group (p<0.01). The BMD in the tooth socket was significantly increased by LPS/High-dose CIAM group compared with the LPS/Vehicle group (p<0.01). In PBS injection group with or without compound, we had no significant result. Conclusion:. TNF receptor antagonist (The CIAM compound) prevented inhibitory effects of LPS on bone formation.