Abstract
Osteoclasts are responsible for bone resorption caused by bone microstructural damage and bone-related disorders. Evidence shows that tanshinone IIA (Tan‑IIA), a traditional Chinese medicine, is used clinically as a drug for the treatment of cardiovascular and cerebrovascular diseases. However, the efficacy and mechanism underlying the effect of Tan‑IIA on the viability of osteoclasts remain to be fully elucidated. The present study investigated the therapeutic effects of Tan‑IIA on osteoblast differentiation and oxidative stress in vitro and in vivo. Cell viability was analyzed and oxidative stress was examined in the osteoblasts. Wnt1sw/sw mice were used to investigate the therapeutic effects of Tan‑IIA on spontaneous tibia fractures and severe osteopenia. The bone strength, collagen and mineral were examined in the tibia. Osteoblast activity was also analyzed in the experimental mice. The Tan‑IIA‑induced differentiation of osteoclasts and the mechanism of action were investigated in osteocytes. The data showed that Tan‑IIA treatment improved cell viability. The data also demonstrated that Tan‑IIA decreased the levels of H2O2, accumulation of reactive oxygen species and apoptosis of osteoblasts. Tan‑IIA inhibited the deleterious outcomes triggered by oxidative stress. In addition, Tan‑IIA inhibited the activation of nuclear factor (NF)‑κB and its target genes, tumor necrosis factor (TNF)‑α, inducible nitric oxide synthase and cyclooxygenase 2, and increased the levels of TNF receptor‑associated factor 1 and inhibitor of apoptosis protein‑1/2 in the osteocytes. Furthermore, it was shown that Tan‑IIA reduced the propensity to fractures and severe osteopenia in mice with osteoporosis. Tan‑IIA also exhibited improved bone strength, mineral and collagen in the bone matrix of the experimental mice. It was found that the Tan‑IIA‑mediated benefits on osteoblast activity and function were through the NF‑κB signaling pathway. Taken together, the data obtained in the present study suggested that Tan‑IIA had protective effects against oxidative stress in osteoblastic differentiation in mice with osteoporosis by regulating the NF‑κB signaling pathway.