Aluminum trichloride inhibits osteoblast mineralization via TGF-β1/Smad signaling pathway

• AlCl3 decreased osteoblast mineralized matrix nodules in vitro.
• AlCl3 inhibited mRNA and protein expressions for components of TGF-β1/Smad pathway.
• AlCl3 increased mRNA expression of Smad7 which is an inhibitor of TGF-β1/Smad pathway.

Osteoporosis is a major global public health problem. Aluminum (Al) exposure inhibits osteoblast mineralization and induces osteoporosis. However, the exact mechanism is not fully understood. The transforming growth factor β1 (TGF-β1)/Smad pathway is a major signaling cascade in regulating osteoblast mineralization. To investigate whether TGF-β1/Smad signaling pathway was involved in the Al-induced inhibition of osteoblast mineralization, osteoblasts were cultured and exposed to different concentrations of aluminum trichloride (AlCl3) (containing 0, 0.01, 0.02 and 0.04 mg/mL Al3+) for 24 h. We found that mineralized matrix nodules, mRNA expressions of alkaline phosphatase (ALP), type I collagen (Col I), TGF-β1, TGF-β type I receptor, TGF-β type II receptor and Smad4, protein expressions of TGF-β1 and p-Smad2/3, Smad2/3/4 trimeric complex were all decreased, whereas the mRNA expressions of Smad7 were increased in the AlCl3-treated groups compared with those in control. In conclusion, these results indicated that AlCl3 inhibited osteoblast mineralization via TGF-β1/Smad signaling pathway in rat osteoblasts. Our findings could provide novel insights into the mechanisms of action of AlCl3 in osteoporosis.