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钙螯合羊骨胶原多肽抑制骨质疏松发生的RANK/RANKL/OPG信号机制
Regulation of RANK/RANKL/OPG Signal Pathway by Calcium Chelated Sheep Bone Collagen Peptide in Inhibiting the Occurrence of Osteoporosis
【摘要】 OPG/RANKL/RANK信号通路在破骨细胞形成过程中起着至关重要的作用,本研究将探讨钙螯合羊骨胶原多肽(SBCP-Ca)对骨质疏松(OP)发生的抑制作用及其基于OPG/RANKL/RANK信号通路的作用机制。通过摘除大鼠双侧卵巢建立OP模型,SBCP-Ca(100mg·mL-1)的灌胃剂量为10mL·(kg·d)-1,持续8周。试验期结束后,股骨远端干骺端扫描电镜观察结果表明OP造模成功。模型组大鼠血液中反映骨形成和吸收的PINP和β-CTx水平均极显著高于假手术组(P<0.01),股骨中的钙含量和羟脯氨酸含量则极显著低于假手术组(P<0.01)。SBCP-Ca组的血清PINP、β-CTx水平则与假手术组无显著差异(P>0.05),股骨中的钙含量和羟脯氨酸含量极显著高于模型组(P<0.01)。荧光定量PCR结果表明模型组股骨组织中RANK和RANKL相对转录水平均极显著高于假手术组(P<0.01),骨质疏松对OPG的表达没有显著影响。SBCP-Ca组的RANK和RANKL极显著低于模型组(P<0.01),OPG水平则极显著高于模型组和假手术组(P<0.01)。以上结果表明:SBCP-Ca可有效抑制OP的发生,通过抑制RANK和RANKL表达,促进OPG表达的三重作用来抑制破骨细胞的形成和骨吸收活性。
【Abstract】 OPG/RANKL/RANK signal pathway plays critical roles in the formation of osteoclasts.Inhibitive roles of calcium chelated sheep bone collagen peptide(SBCP-Ca)in the development of osteoporosis(OP)and its mechanism based on the OPG/RANKL/RANK signal pathway were investigated in this study.OP models of SD rats were established by bilateral ovariectomy.SBCP-Ca(100 mg·mL-1)was intragastrically administered at 10 mL·(kg·d)-1 for 8 weeks.After treatment,scanning electron microscopy for metaphysis of distal femur showed that OPmodels were successfully established.The serum levels of PINP andβ-CTx,which reflected bone formation and bone resorption respectively,were significantly higher in model group(P<0.01),while the calcium and proline contents in femur bone were significantly lower than the sham group(P<0.01).The levels of PINP andβ-CTx in SBCP-Ca group showed no statistical differences compared with the sham group(P>0.05),both Ca and proline content were higher than that of the model group(P<0.01).The results of real-time PCR suggested that the relative mRNA levels of RANKand RANKLin model group were significantly higher than that of the sham group(P<0.01),while the expression of OPG showed no significant changes.The results showed that the transcriptional levels of RANK and RANKL were significantly lower in SBCPCa group than that of the model group(P<0.01),and the OPG level was significantly higher than that of the other groups(P<0.01).It can be concluded that SBCP-Ca could inhibit the occurrence of osteoporosis effectively by inhibiting the expression of RANK and RANKL,and promoting the expression of OPGin bone tissue.The triple actions of SBCP-Ca inhibited the formation and the resorption activity of osteoclasts.
【Key words】 osteoporosis; osteoclasts; PINP; β-CTx; RANK/RANKL/OPG signal pathway;
- 【文献出处】 畜牧兽医学报 ,Chinese Journal of Animal and Veterinary Sciences , 编辑部邮箱 ,2018年05期
- 【分类号】S856.5
- 【被引频次】7
- 【下载频次】213