miR-33a promotes peri-implantitis by facilitating M1-type polarization of macrophages and inhibiting osteogenesis.

miR-33a exhibits abnormal expression in patients with periodontitis. However, the underlying mechanism of miR-33a in peri-implantitis remains elusive. This study centered on investigating the mechanism of the miR-33a/SIRT6 axis in peri-implantitis. First, compare the expression levels of miR-33a in peri-implantitis tissues and healthy tissues. Second, examine the impacts of miR-33a on ALP, osteogenic markers (RUNX2, BMP-2, OCN, COL1A1), and M1-type markers (CD86, INOS, TNF-α, IL-6) in periodontal ligament stem cells (PDLSCs) or M1-type macrophages. Moreover, the effect of polarization on osteogenesis was explored by culturing PDLSCs in a medium obtained from M1-type macrophages. Finally, the regulatory effect of miR-33a on SIRT6 was validated via a dual luciferase reporter assay, and the influence of the miR-33a/SIRT6 axis on osteogenesis and macrophage polarization was investigated. In clinical investigations, the expression level of miR-33a was elevated in the peri-implantitis tissues. In PDLSCs, the overexpression of miR-33a led to a reduction in the activity of ALP and the expression of osteogenic factors at both the mRNA and protein levels. Nevertheless, as the downstream target of miR-33a, SIRT6 exerted a potent promotional effect on osteogenesis. The M1-type polarization of macrophages impeded osteogenic differentiation. Furthermore, the miR-33a/SIRT6 axis also played a regulatory role in the polarization. Inhibiting miR-33a significantly downregulated the expression of M1 markers in macrophages by upregulating SIRT6. Peri-implantitis may be associated with miR-33a. The miR-33a/SIRT6 axis might participate in the development of peri-implantitis through the regulation of periodontal bone formation and the bone immune microenvironment.