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The purpose of this study was to explore the effect of periostin on autophagy and factors related to bone metabolism in osteoblasts. According to experimental design, some osteoblast-like cells (MC3T3-E1) were transfected by lentiviral vector to silence periostin gene. Celigo® Image Cytometer and Real-Time PCR were used to assess target gene silencing effects. Western blotting was used to evaluate autophagy-associated factors (LC3B,Beclin1) and factors related to bone metabolism (RANKL, OPG, NF-κBP65). Another part of osteoblasts was added with recombinant periostin protein at concentration of 75ng/mL. Monodansylcadaverine (MDC) detection was conducted to trace formation of autophagy vesicles. Factors associated with autophagy and bone metabolism were reassessed using western blotting. When periostin gene was silenced, western blotting analysis showed that the expression of LC3B-I, Beclin1, RANKL and NF-κBP65 in experimental group was significantly increased; however, OPG expression was decreased. After adding recombinant periostin protein, MDC detection revealed significantly fewer green fluorescent particles in the experimental group. Western blotting results showed that the expression of LC3B, Beclin1, RANKL and NF-κBP65 was decreased; however, OPG expression was increased. This study examined the regulatory mechanism of periostin in bone metabolism, which will provide a future reference for the treatment of primary teeth abnormal replacement caused by inflammation.