Autophagy negative-regulating Wnt signaling enhanced inflammatory osteoclastogenesis from Pre-OCs in vitro - 19/04/20
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Highlights |
• | Dual effects of lipopolysaccharide were found on osteoclastogenesis in vitro. |
• | Lipopolysaccharide promoted osteoclasts differentiation only from RANKL primed cells. |
• | Effects of autophagy and Wnt signaling were demonstrated in lipopolysaccharide induced osteoclastogenensis. |
• | A crosstalk between autophagy and Wnt signaling was elucidated during osteoclast differentiation. |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Osteoclast, Lipopolysaccharide, Autophagy, Wnt signaling
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Article 110093- juin 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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