鲫鱼卵唾液酸糖蛋白抑制小鼠破骨细胞的分化机制研究  

Study on the mechanisms of Carassius auratus sialoglycoproteins in suppressing the differentiation of osteoclast

作　　者：于哲[1] 王静凤[1] 毛磊[1] 周晓春[1] 薛长湖[1] 

机构地区：[1]中国海洋大学食品科学与工程学院,山东青岛266003

出　　处：《中国海洋药物》2015年第5期33-40,共8页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(31371876;31471684;U1406402)资助

摘　　要：目的探讨鲫鱼卵唾液酸糖蛋白(Carassius auratus sialoglycoproteins,Ca-SGP)对核因子κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)诱导形成的破骨细胞的抑制作用及机制。方法初断乳ICR雄性小鼠,无菌取股骨,分离骨髓造血细胞并诱导其分化为破骨细胞。分别检测Ca-SGP对破骨细胞及其前体细胞活力、抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)活性及分化成熟过程的影响,测定破骨细胞形成过程中核因子κB(Nuclear factor,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路关键因子的表达。结果 Ca-SGP可有效抑制由RANKL诱导的破骨细胞分化及成熟,降低细胞TRAP活性及其表达,抑制骨吸收陷窝形成;分子机制方面,Ca-SGP可明显降低信号传导关键蛋白TRAP6的活性,进而抑制NF-κB和MAPKs信号通路关键因子mRNA的表达,达到抑制破骨细胞分化成熟的效果。结论 Ca-SGP可通过NF-κB和MAPKs信号通路抑制由RANKL诱导的破骨细胞形成和分化成熟。Objective To investigate the effects of Ca-SGP on the RANKL-induced osteoclastogenesis and signaling pathways. Methods Osteoclast was differentiated from mouse bone marrow-derived macropha- ges（BMMs） with M-CSF and RANKL. Osteoclast and its precursor activity were measured by MTT. Osteoclast numbers were evaluated by TRAP stains, mRNA levels were analyzed by qRT-PCR. Results Ca-SGP inhibited the osteoclast differentiation without toxicity, and reduced the generation of TRAP- positive multinucleated cells by suppressing MAPK and NF-κB signaling pathways. Conclusion Ca-SGP suppressed osteoclastogenesis through inhibiting RANKL-induced MAPKs and NF-κB pathway.

关 键 词：鲫鱼卵唾液酸糖蛋白 抗酒石酸酸性磷酸酶 核因子ΚB 丝裂原活化蛋白激酶 

分 类 号：R965[医药卫生—药理学]