Abstract
Staphylococcus aureus (S. aureus) is the most common organism causing osteomyelitis, and Staphylococcus aureus protein A (SpA) is an important virulence factor anchored in its cell wall. However, the precise mechanisms underlying the bone loss caused by SpA have not been well understood. The present study aimed to investigate the effect of SpA on osteoclast differentiation, and the probable mechanism was investigated. Raw264.7 cells were treated with SpA in the absence or presence of receptor‑activated (NF)‑κB ligand for 5 days, and morphological and biochemical assays were used to assess osteoclastogenesis and explore the underlying mechanisms. Data demonstrated that SpA induced osteoclast differentiation and promoted bone resorption in a dose‑dependent manner in the absence or presence of RANKL. In addition, the expression of osteoclast‑specific genes, such as the tartrate resistant acid phosphatase, matrix metalloproteinase‑9, cathepsin K, calcitonin receptors and d2 isoform of the vacuolar ATPase Vo domain, were enhanced by SpA. Furthermore, the SpA‑induced osteoclast differentiation was associated with the degradation of inhibitor of κB‑α, phosphorylation of NF‑κB p65 and increased expression of nuclear factor of activated T‑cells. However, by treatment with JSH‑23, an NF‑κB inhibitor, the formation of osteoclast‑like cells and resorption pits was significantly reduced, and the expression of osteoclast‑specific genes was also inhibited. Collectively, in the present study SpA induced osteoclast differentiation, promoted bone resorption, and the NF‑κB signaling pathway was involved in this process.