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

doi:10.11843/j.issn.0366-6964.2018.05.020

畜牧兽医学报 ›› 2018, Vol. 49 ›› Issue (5): 1047-1053.doi: 10.11843/j.issn.0366-6964.2018.05.020

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

韩克光¹, 申勇涛¹, 原恺¹, 范华², 陈静¹, 金淑秀¹, 古少鹏¹, 田文霞¹, 张鼎¹, 霍乃蕊^1*, 常泓^3*

1. 山西农业大学动物科技学院, 太谷 030801;
2. 山西农业大学实验中心, 太谷 030801;
3. 山西农业大学生命科学院, 太谷 030801

收稿日期:2017-10-09 出版日期:2018-05-23 发布日期:2018-05-23
通讯作者: 霍乃蕊,女,山西平遥人,博士,教授,主要从事动物疾病预防与动物性食品安全研究,E-mail:tgnrhuo@163.com;常泓,女,山西榆次人,博士,教授,主要从事食品安全和分子生物学研究,E-mail:941004578@qq.com
作者简介:韩克光,男,山西祁县人,副教授,硕士,主要从事兽医药物代谢与药效研究,E-mail:sxndkghan@163.com;申勇涛,山西黎城人,硕士生,主要从事兽医公共卫生研究,E-mail:2292192900@qq.com
基金资助:
国家自然科学基金（31201347）；山西省回国留学人员项目（2014-042）

Regulation of RANK/RANKL/OPG Signal Pathway by Calcium Chelated Sheep Bone Collagen Peptide in Inhibiting the Occurrence of Osteoporosis

HAN Ke-guang¹, SHEN Yong-tao¹, YUAN Kai¹, FAN Hua², CHEN Jing¹, JIN Shu-xiu¹, GU Shao-peng¹, TIAN Wen-xia¹, ZHANG Ding¹, HUO Nai-rui^1*, CHANG Hong^3*

1. College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China;
2. Shanxi Agricultural University Experimental Center, Taigu 030801, China;
3. College of Life Science, Shanxi Agricultural University, Taigu 030801, China

Received:2017-10-09 Online:2018-05-23 Published:2018-05-23

摘要/Abstract

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 （100 mg·mL^-1）的灌胃剂量为10 mL·（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 OP models were successfully established. The serum levels of PINP and β-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 and β-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 RANK and RANKL in 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 SBCP-Ca 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 OPG in bone tissue. The triple actions of SBCP-Ca inhibited the formation and the resorption activity of osteoclasts.

中图分类号:

S857.16

韩克光, 申勇涛, 原恺, 范华, 陈静, 金淑秀, 古少鹏, 田文霞, 张鼎, 霍乃蕊, 常泓. 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[J]. 畜牧兽医学报, 2018, 49(5): 1047-1053.

HAN Ke-guang, SHEN Yong-tao, YUAN Kai, FAN Hua, CHEN Jing, JIN Shu-xiu, GU Shao-peng, TIAN Wen-xia, ZHANG Ding, HUO Nai-rui, CHANG Hong. Regulation of RANK/RANKL/OPG Signal Pathway by Calcium Chelated Sheep Bone Collagen Peptide in Inhibiting the Occurrence of Osteoporosis[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(5): 1047-1053.

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参考文献

[1] 吕文亭, 马利芹, 杨永红, 等. 低钙日粮添加依普黄酮对笼养蛋鸡骨组织显微结构和形态计量学的影响[J]. 畜牧兽医学报, 2012, 43(11):1818-1824.
LV W T, MA L Q, YANG Y H, et al. Effects of adding ipriflavone to low-calcium diet on microstructure and histomorphometry of bone in cage layers[J]. Acta Veterinaria et Zootechnica Sinica, 2012, 43(11):1818-1824. (in Chinese)
[2] DVORAK G, GRUBER R, HUBER C D, et al. Trabecular bone structures in the edentulous diastema of osteoporotic sheep[J]. J Dent Res, 2008, 87(9):866-870.
[3] WEBSTER A B. Welfare implications of avian osteoporosis[J]. Poult Sci, 2004, 83(2):184-192.
[4] 赵文韬, 张晓刚, 王志鹏. 自噬与骨质疏松症的相关性[J]. 中国生物化学与分子生物学报, 2017, 33(4):337-341.
ZHAO W T, ZHANG X G, WANG Z P. Relationship between autophagy and osteoporosis[J]. Chinese Journal of Biochemistry and Molecular Biology, 2017, 33(4):337-341. (in Chinese)
[5] 元宇, 仝晓阳, 邹军. miR-214对骨形成的抑制作用[J]. 中国生物化学与分子生物学报, 2017, 33(2):133-137.
YUAN Y, TONG X Y, ZOU J. The Roles of miR-214 in inhibition of bone formation[J]. Chinese Journal of Biochemistry and Molecular Biology, 2017, 33(2):133-137. (in Chinese)
[6] GUÉGUEN L, POINTILLART A. The bioavailability of dietary calcium[J]. J Am Coll Nutr, 2000, 19(2 Suppl):119S-136S.
[7] BRONSKY J, PRUŠA R, NEVORAL J. The role of amylin and related peptides in osteoporosis[J]. Clin Chim Acta, 2006, 373(1-2):9-16.
[8] 刘继中, 纪宗玲, 陈苏民. OPG/RANKL/RANK系统与骨破坏性疾病[J]. 生物工程学报, 2003, 19(6):655-660.
LIU J Z, JI Z L, CHEN S M. The OPG/RANKL/RANK system and bone resorptive disease[J]. Chinese Journal of Biotechnology, 2003, 19(6):655-660. (in Chinese)
[9] VARLEY I, HUGHES D C, GREEVES J P, et al. RANK/RANKL/OPG pathway:genetic associations with stress fracture period prevalence in elite athletes[J]. Bone, 2015, 71:131-136.
[10] TU P, DUAN P, ZHANG R S, et al. Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women[J]. Osteoporos Int, 2015, 26(1):179-185.
[11] OHLSSON C, VANDENPUT L. The role of estrogens for male bone health[J]. Eur J Endocrinol, 2009, 160(6):883-889.
[12] 尹鑫, 于海龙, 李青春, 等. 补肾中药对OPG/RANK/RANKL系统调控作用的研究进展[J]. 承德医学院学报, 2016, 33(2):126-129.
YIN X, YU H L, LI Q C, et al. Research progress on regulation of kidney-tonifying herbs on OPG/RANK/RANKL system[J]. Journal of Chengde Medical College, 2016, 33(2):126-129. (in Chinese)
[13] 高文伟, 申勇涛, 程稚玲, 等. 钙螯合胶原多肽与雌激素对去卵巢大鼠骨质改善作用的比较[J]. 中国实验动物学报, 2017, 25(3):256-262.
GAO W W, SHEN Y T, CHENG Z L, et al. Comparison of the ameliorating effect of collagen peptide chelated calcium and estrogen on the bone quality in ovariectomized rats[J]. Acta Laboratorium Animalis Scientia Sinica, 2017, 25(3):256-262. (in Chinese)
[14] 韩克光, 甄守艳, 范华, 等. 钙螯合羊骨胶原多肽的制备及表征分析[J]. 农业工程学报, 2015, 31(21):301-307.
HAN K G, ZHEN S Y, FAN H, et al. Preparation and characteristic analysis of calcium-chelated ossein peptide[J]. Transactions of the Chinese Society of Agricultural Engineering, 2015, 31(21):301-307. (in Chinese)
[15] 张铁军, 张伟, 边立功, 等. 白藜芦醇对去卵巢大鼠骨质疏松症的保护作用[J]. 解剖学报, 2012, 43(5):679-684.
ZHANG T J, ZHANG W, BIAN L G, et al. Protective effects and mechanisms of resveratrol on the rats suffering with osteoporosis[J]. Acta Anatomica Sinica, 2012, 43(5):679-684. (in Chinese)
[16] 何蕾, 薛仁宇, 曹广力, 等. 基于RNA-Seq技术分析家蚕卵巢培养细胞(BmN)高表达基因[J]. 蚕业科学, 2014, 40(3):409-421.
HE L, XUE R Y, CAO G L, et al. Analysis of highly expressed genes in Bombyx mori ovarian culture cells(BmN)based on RNA-Seq technology[J]. Science of Sericulture, 2014, 40(3):409-421. (in Chinese)
[17] 李艳敏, 李翠翠, 郑航, 等. 雌激素通过ER-α调控CYP2C8在鸡肝中的表达[J]. 畜牧兽医学报, 2016, 47(12):2362-2369.
LI Y M, LI C C, ZHENG H, et al. Expression of CYP2C8 is regulated by estrogen through ER-α in liver of chicken[J]. Acta Veterinaria et Zootechnica Sinica, 2016, 47(12):2362-2369. (in Chinese)
[18] 赵兵令, 王海东, 陈天直, 等. 小鼠毛囊不同生长周期中MITF下游色素相关基因的定位表达及相关性分析[J]. 中国生物化学与分子生物学报, 2017, 33(2):198-206.
ZHAO B L, WANG H D, CHEN T Z, et al. Localization and correlation analysis of MITF downstream pigmentation-related genes at different growth cycle of mouse hair follicle[J]. Chinese Journal of Biochemistry and Molecular Biology, 2017, 33(2):198-206. (in Chinese)
[19] 陈玮. 中青年Graves病患者血清PINP及β-CTx与骨代谢关系分析[D]. 合肥:安徽医科大学, 2013.
CHEN W. Analysis of the relationship between PINP、β-CTx and bone metabolism in young adult patients with Graves' disease[D]. Hefei:Anhui Medical University, 2013. (in Chinese)
[20] KOIVULA M K, RISTELI L, RISTELI J. Measurement of aminoterminal propeptide of type I procollagen (PINP) in serum[J]. Clin Biochem, 2012, 45(12):920-927.
[21] VASIKARAN S, COOPER C, EASTELL R, et al. International osteoporosis foundation and international federation of clinical chemistry and laboratory medicine position on bone marker standards in osteoporosis[J]. Clin Chem Lab Med, 2011, 49(8):1271-1274.
[22] 黄云梅. 基于RANKL/RANK/OPG轴的绝经后骨质疏松症发病机制及健骨颗粒干预研究[D]. 福州:福建中医药大学, 2014.
HUANG Y M. Study on pathogenesis of postmenopausal osteoporosis and effect of Jiangu granule based on OPG/RANKL/RANK System[D]. Fuzhou:Fujian University of Traditional Chinese Medicine, 2014. (in Chinese)
[23] 刘康, 吴风晴, 吴连国, 等. 骨碎补总黄酮对骨质疏松模型大鼠OPG/RANKL/RANK轴系统的影响[J]. 中国现代应用药学, 2015, 32(6):652-656.
LIU K, WU F Q, WU L G, et al. Effect on OPG/RANKL/RANK axial system in osteoporotic rats by total flavones of drynariae rhizoma[J]. Chinese Journal of Modern Applied Pharmacy, 2015, 32(6):652-656. (in Chinese)
[24] 李子怡, 李玉坤. OPG/RANK/RANKL信号通路在骨质疏松症中的研究进展和应用[J]. 中华老年骨科与康复电子杂志, 2017, 3(2):124-128.
LI Z Y, LI Y K. Researching progress and application of OPG-RANK-RANKL signaling pathway in osteoporosis[J]. Chinese Journal of Geriatric Orthopaedics and Rehbilitation (Electronic Edition), 2017, 3(2):124-128. (in Chinese)

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

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