全氟辛酸对成骨细胞骨形成和破骨细胞骨吸收作用研究  

Effects of PFOA on osteoblastic bone formation and osteoclastic bone resorption

作　　者：薛黎明[1] 林元杰 金玉娥[1] 徐佳乐 卢大胜[1] 汪国权[1] Liming Xue;Yuanjie Lin;Yu’e Jin;Jiale Xu;Dasheng Lu;Guoquan Wang(State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants,Shanghai Municipal Center for Disease Control and Prevention,Shanghai 200336,China)

机构地区：[1]上海市疾病预防控制中心,国家环境保护新型污染物环境健康影响评价重点实验室,上海200336

出　　处：《日用化学工业（中英文）》2024年第6期648-655,共8页China Surfactant Detergent & Cosmetics

基　　金：上海市自然科学基金面上项目(21ZR1454600,22ZR1453400);上海市“医苑新星”青年医学人才-公共卫生领导者项目(沪卫人事[2021]99号);上海市卫生健康委员会面上项目(202040208);上海市社会发展科技攻关项目(21DZ1202100);上海市加强公共卫生体系建设三年行动计划(2023-2025年)重点学科(GWVI-11.1-41)

摘　　要：考察全氟辛酸(PFOA)对成骨细胞骨形成和破骨细胞骨吸收的作用和机制,为探索PFOA暴露引起骨丢失提供科学依据。采用原代新生大鼠颅盖骨分离成骨细胞,考察1,10和100μmol/L PFOA对成骨细胞增殖,碱性磷酸酶(ALP)活性和骨结节形成的影响;采用巨噬细胞集落刺激因子(M-CSF)及核因子κB受体激活因子配体(RANKL)诱导大鼠骨髓单核细胞分化破骨细胞模型,考察1,10和100μmol/L PFOA对破骨细胞活力,抗酒石酸酸性磷酸酶(TRAP)活性和骨吸收陷窝形成指标的影响;采用Western blot考察成骨细胞护骨素(OPG)和RANKL蛋白表达。PFOA在1和10μmol/L时促进成骨细胞活力,但对ALP活性和骨结节形成无影响。100μmol/L PFOA可显著抑制细胞增殖,ALP活性和骨结节形成,同时抑制OPG/RANKL蛋白表达的比例。PFOA对破骨细胞活力无影响,10和100μmol/L PFOA可显著抑制促进TRAP活性和骨吸收陷窝形成面积。PFOA抑制成骨细胞骨形成作用可能通过下调Wnt通路,通过抑制OPG/RANKL/RANK通路,促进破骨细胞骨吸收作用。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 100μmol/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 factorκB 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 1μmol/L and 10μmol/L can promote osteoblast proliferation,but has no effect on ALP activity and bone nodule formation.100μmol/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 10μmol/L and 100μmol/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.

关 键 词：全氟辛酸 骨丢失 成骨细胞 破骨细胞 OPG/RANKL/RANK通路 

分 类 号：TQ658[化学工程—精细化工]