Department of Periodontology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, PR China.
Department of Periodontology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, PR China; Cancer Institute, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, PR China.
Biomed Pharmacother. 2020 Jun;126:110093. doi: 10.1016/j.biopha.2020.110093. Epub 2020 Mar 18.
Periodontitis thereby the alveolar bone loss induced by inflammation, is a wide-spread phenomenon around the world. It is an ongoing challenge faced by clinicians worldwide. This study aimed to identify the effects of lipopolysaccharide (LPS) on osteoclasts (OCs) differentiation in vitro and to investigate its molecular mechanism. For bone marrow derived macrophages (considered as Pro-OCs), LPS impaired their differentiation into OCs in a dose-dependent manner. In contrast, it promoted Pre-OCs (referred to receptor activator of nuclear factor-κB ligand (RANKL) pretreated Pro-OCs) and differentiated to OCs with increased maximum diameter, quantity, the covering area and the fusion index in vitro. It also facilitated OCs proliferation, bone resorption and OCs related genes expression. Furthermore, it was revealed that LPS enhanced OCs genesis from Pre-OCs via activating autophagy pathway consequently elevated the accumulation of TRAP, Cts K and NFATC1, specific genes of OCs. The members of Wnt signaling were expressed as at lower states during the LPS induced OCs formation, but they could be rescued in the presence of autophagy inhibitor. The most promising observation was the direct interaction of LC3B and Dvl2, indicating that the crosstalk between above pathways existed in OCs. Taken together, we consider that LPS activates autophagy which negatively regulates Wnt signaling via autophagic degradation of Dvl2 is significant for osteoclastogenesis from Pre-OCs in vitro. Our study sheds light on the fact that autophagy inhibitors will become a new, potentially applicable therapeutic option in the treatment of periodontal bone loss.
牙周炎是一种由炎症引起的牙槽骨丧失的广泛现象，在世界各地都很普遍。这是全球临床医生面临的一个持续挑战。本研究旨在确定脂多糖 (LPS) 对体外破骨细胞 (OC) 分化的影响，并探讨其分子机制。对于骨髓来源的巨噬细胞（被认为是前破骨细胞，Pro-OCs），LPS 以剂量依赖的方式损害它们向 OC 的分化。相比之下，它促进了 Pre-OCs（称为核因子-κB 配体 (RANKL) 预处理的 Pro-OCs）的分化，并通过增加最大直径、数量、覆盖面积和融合指数来促进 OC 的分化。它还促进了 OC 的增殖、骨吸收和 OC 相关基因的表达。此外，研究表明 LPS 通过激活自噬途径增强 Pre-OCs 向 OC 的发生，从而增加了 TRAP、Cts K 和 NFATC1 的积累，这些都是 OC 的特异性基因。在 LPS 诱导的 OC 形成过程中，Wnt 信号通路的成员表达水平较低，但在自噬抑制剂存在的情况下可以得到恢复。最有希望的观察结果是 LC3B 和 Dvl2 的直接相互作用，表明上述途径之间存在串扰。总之，我们认为 LPS 通过自噬降解 Dvl2 激活自噬，从而负调控 Wnt 信号通路，这对于体外 Pre-OCs 向破骨细胞的分化具有重要意义。我们的研究表明，自噬抑制剂将成为治疗牙周骨丢失的一种新的、潜在的应用治疗选择。
