Syndecan 4 contributes to osteoclast differentiation induced by RANKL through enhancing autophagy.

Abstract

Periodontitis is a common chronic disease. Osteoclast differentiation contributes to alveolar bone resorption which is a distinct phenomenon during periodontitis. Syndecan 4 (SDC4), a member of the syndecan family, was found to be highly expressed during periodontitis. However, little is known about its role in periodontitis. Herein, we explored the role of SDC4 in osteoclast differentiation. An experimental periodontitis rat model was established by ligating the right first molar. The SDC4 expression in periodontium was detected by western blot and immunofluorescence. Our study demonstrated that SDC4 was highly expressed in the periodontium of periodontitis rats. It was positively transcriptionally regulated by NF-κB. SDC4 silencing abrogated osteoclast differentiation induced by RANKL, while SDC4 overexpression enhanced osteoclast differentiation. Moreover, SDC4 enhanced autophagy induced by RANKL. 3-MA, an autophagy inhibitor, was employed to explore whether SDC4 impacts osteoclast differentiation through activating autophagy. Treatment with 3-MA abolished osteoclast differentiation which was enhanced by SDC4, indicating that SDC4 promotes osteoclast differentiation through activating autophagy. This study reveals that SDC4 may contribute to osteoclast differentiation during periodontitis through activating autophagy. It sheds light on the important role of SDC4 in periodontitis.