Yam Carbon Dots Promote Bone Defect Repair by Modulating Histone Demethylase 4B

QianYang Chen,1,* Shuo Liu,1,* Yuhan Wang,1,* MeiChen Tong,2 HaiBo Sun,2 Ming Dong,1 Yun Lu,1 WeiDong Niu,1 LiNa Wang1 1Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 2Academician Laboratory of Immune and Oral Development & Regeneration, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China*These authors contributed equally to this workCorrespondence: WeiDong Niu; LiNa Wang, Email [email protected]; [email protected]: Chronic apical periodontitis is a typical inflammatory disease of the oral cavity, the pathology is characterized by an inflammatory reaction with bone defects in the periapical area. Chinese medicine is our traditional medicine, Carbon Dots (CDs) are a new type of nanomaterials. The purpose of this study was to prepare Yam Carbon Dots (YAM-CDs) to investigate the mechanism of action of YAM-CDs on bone differentiation in vivo and in vitro.Methods: We characterized YAM-CDs using transmission electron microscopy (TEM), Fourier Transform Infrared Spectrometer (FTIR), X-Ray Diffraction (XRD) and photoluminescence (PL). CCK-8 assay, Real-time qPCR, and Western Blot were conducted using bone marrow mesenchymal stem cells (BMSCs) to verify that YAM-CDs promote osteoblast differentiation. In addition, we investigated the role of YAM-CDs in promoting bone formation in an inflammatory setting in an in vivo mouse model of cranial defects.Results: The results of TEM and PL showed that the YAM-CDs mostly consisted of the components C1s, O1s, and N1s. Additionally the average sizes of YAM-CDs were 2– 6 nm. The quantum yield was 4.44%, with good fluorescence stability and biosafety. Real-time qPCR and Western blot analysis showed that YAM-CDs promoted osteoblast differentiation under an inflammatory environment by regulating expression of histone demethylase 4B (KDM4B). In vivo, results showed that YAM-CDs effectively repaired cranial bone defects in a mouse model and reduced the expression of inflammatory factors under the action of lipopolysaccharides (LPS).Conclusion: YAM-CDs promoted the proliferation and differentiation of osteoblasts by regulating the expression of KDM4B to repair cranial bone defects in mice under an LPS-induced inflammatory milieu, which will provide a new idea for the treatment of clinical periapical inflammation and other bone defect diseases.Keywords: traditional Chinese medicine, carbon dots, YAM, bone defect, KDM4B