Abstract:

Perfluorooctanoic acid （PFOA） exposure level in human is negatively correlated with bone density according to the epidemiological research. Our study is aim to investigate the effects and mechanisms of PFOA on osteoblastic bone formation and osteoclastic bone resorption. Primary osteoblasts were isolated from the calvaria of newborn rats, and the cell proliferation, alkaline phosphatase （ALP） activity, and bone nodule formation were detected after 1, 10, and 100 μmol/L PFOA treateatment for 24 h.The osteoclasts model were differentiation from bone marrow monocyte, which induced by Macrophage colony-stimulating factor （M-CSF） and Nuclear factor κB receptor-activating factor ligand （RANKL）, and the effects on cell viability, anti-tartaric acid phosphatase （TRAP） activity, and bone resorption pit formation were investigated. The expression of OPG and RANKL proteins in osteoblasts were conducted by Western blot. The results show that PFOA at the concentration of 1 μmol/L and 10 μmol/L can promote osteoblast proliferation, but has no effect on ALP activity and bone nodule formation. 100 μmol/L PFOA can significantly inhibit cell proliferation, ALP activity, and bone nodule formation, as well as the proportion of OPG/RANKL protein expression. PFOA has no effect on osteoclast viability, and 10 μmol/L and 100 μmol/L PFOA can significantly inhibit the TRAP activity and the area of bone resorption pits. The conclusion can be draw that high concentration of PFOA can inhibit the bone formation of osteoblasts by suppressing WNT pathway and promote osteoclast bone resorption by inhibiting the OPG/RANKL/RANK pathway.

Key words: perfluorooctanoic acid, bone loss, osteoblast, osteoclast, OPG/RANKL/RANK pathway