Interleukin-17A facilitates osteoclast differentiation and bone resorption via activation of autophagy in mouse bone marrow macrophages

Abstract

Interleukin 17A (H-17A) exerts pleiotropic effects on periodontitis, partially through enhancement of alveolar bone loss. Osteoclasts are the main culprits that absorb alveolar bone. However, studies describing the correlation between IL-17A and osteoclasts are not conclusive. Previously, autophagy was revealed to be involved in osteoclast differentiation and bone resorption. However, the role of autophagy in IL-i7A-mediated osteoclast formation is yet to be clarified. In the present study, bone marrow macrophages (BMMs) were treated with or without H-17A. 3-Methyladenine (3-MA) was applied to inhibit autophagy. Osteoclast formation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence, and scanning electron microscope. The effects of IL-17A on osteoclast-specific genes and autophagy-related genes during osteoclast differentiation were examined by real-time quantitative polymerase chain reaction and western blot analysis. Autophagosomes were observed by transmission electron microscope. Hematoxylin and eosin (H&E), and TRAP staining was adopted to assess alveolar bone destruction and the number of osteoclasts, respectively in a rat periodontitis model. Consequently, H-17A stimulated osteoclast differentiation and bone resorption of BMMs accompanied by an increase in the mRNA expression of osteoclast-specific genes. Furthermore, IL-17A increased the levels of autophagy-related genes and proteins, and inhibition of autophagy with 3-MA attenuated the H-HA-mediated osteoclastogenesis. In addition, there was an increase in the number of osteoclasts and alveolar bone resorption with H-17A treatment in the periodontitis rat model. Collectively, these findings indicated that H-17A facilitated osteoclast differentiation and bone resorption in vitro and in vivo, which may contribute to the understanding of the molecular basis of H-17A in alveolar bone destruction and provide insight on the clinical therapeutic targets for periodontitis.