TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation.

Previous studies showed that inflammatory cytokines promote osteoclast formation, characterized by the function of bone resorption. However, it remains unclear whether inflammatory factors contribute to osteoporosis syndrome in postmenopausal women. Here, we found that postmenopausal women with osteoporosis (PO) had increased levels of TNF-α, compared with those without osteoporosis. TNF-α is highly correlated with the RANK and estrogen levels in PO patients. in vitro, TNF-α synergistically promotes RANKL-induced osteoclast formation by activation of NF-κB and PI3K/Akt signaling. Moreover, inhibition of PI3K/Akt totally blocked the synergistic effects of TNF-α on NF-κB activation as well as osteoclast formation. Together, these results demonstrate that TNF-α synergistically promotes RANKL-induced osteoclasts formation through activation of PI3K/Akt signaling, which ultimately contributes to osteoporosis syndrome in postmenopausal women.