您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (7): 8-12.doi: 10.6040/j.issn.1671-7554.0.2015.375

• 基础医学 • 上一篇    下一篇

成骨细胞刺激因子对去卵巢骨质疏松大鼠的治疗效果

冯潇雨1, 张洪美2, 车选强1, 康东红3   

  1. 1. 山东大学医学院, 山东 济南 250012;
    2. 淄博市中心医院内分泌科, 山东 淄博 255036;
    3. 山东大学附属千佛山医院内分泌科, 山东 济南 250014
  • 收稿日期:2015-04-13 修回日期:2015-05-18 出版日期:2015-07-10 发布日期:2015-07-10
  • 通讯作者: 康东红。E-mail: kdh_2010@163.com E-mail:kdh_2010@163.com
  • 基金资助:
    山东省优秀中青年科学家科研奖励基金(2004BS02020)

Therapeutic effects of human osteoblast-stimulating factor on osteoporosis of ovariectomized rats

FENG Xiaoyu1, ZHANG Hongmei2, CHE Xuanqiang1, KANG Donghong3   

  1. 1. School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Endocrinology, Central Hospital of Zibo, Zibo 255036, Shandong, China;
    3. Department of Endocrinology, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2015-04-13 Revised:2015-05-18 Online:2015-07-10 Published:2015-07-10

PDF (PC)

249

摘要： 目的 观察人成骨细胞刺激因子(OSF-1)对去卵巢骨质疏松大鼠的治疗效果。方法 健康4月龄SD雌性大鼠12只, 随机分为假手术组(SHAM组)、去势组(OVX组)、甲状旁腺激素组(PTH组)和OSF-1组, 每组3只。SHAM组切除卵巢附近脂肪组织, 其他各组切除双侧卵巢。术后10周, SHAM组和OVX组皮下注射生理盐水, 0.2 mL/d, PTH组皮下注射PTH, 20 μg/(kg·d), OSF-1组皮下注射OSF-1, 80 μg/(kg·d)。术后21周, 处死大鼠, 分离子宫并称重, 分离股骨, 显微CT扫描干骺端。结果 OVX组子宫重和骨量较SHAM组显著降低(P<0.01), 骨小梁微结构明显破坏。与OVX组相比, PTH组和OSF-1组的骨密度、骨体积分数、骨小梁数量显著增加(P<0.01), 骨小梁分离度和模式因子显著下降(P<0.01, P<0.05), 骨小梁微结构更紧密。PTH组较OSF-1组骨密度、骨体积分数、骨小梁数量显著增加(P<0.01), 骨小梁模式因子显著下降(P<0.01)。结论 皮下注射OSF-1[80 μg/(kg·d)]可有效增加去卵巢大鼠的骨量, 改善骨小梁微结构。

关键词: 成骨细胞刺激因子, 绝经后骨质疏松, 卵巢切除大鼠, 显微CT

Abstract: Objective To investigate the therapeutic effects of human osteoblast-stimulating factor (OSF-1) on the osteoporosis of ovariectomized rats. Methods A total of 12 female rats aged 4 months were randomly divided into 4 groups: SHAM group, OVX group, human parathyroid hormone group (PTH group) and OSF-1 group. A small piece of adipose tissue was cut off from rats in SHAM group; bilateral ovariectomy was conducted in rats in the other groups. All rats were intervened per day separately since 10 weeks after the ovariectomy: SHAM and OVX groups received subcutaneous injection of 0.2 mL/d sodium chloride solution, PTH group was given subcutaneous injection of 20 μg/(kg·d) PTH, and OSF-1 group was injected subcutaneously with 80 μg/(kg·d) OSF-1. Pharmacological agents were administrated consecutively for 11 weeks, then all rats were sacrificed. Uterus was removed and weighed. Femur was removed and cleaned of adhering muscles and connective tissues. Microcomputed tomography (micro-CT) was used to scan proximal femur metaphysis. Results Uterus weight and bone mass in OVX group were significantly lower than those in SHAM group (P<0.01), and the microstructure of bone trabecula was destructed in OVX group. Compared with OVX group, bone morphometric parameters in PTH and OSF-1 groups showed significant increase on bone mineral density(BMD), BV/TV, Tb.N(P<0.01), while Tb.Sp and TBPf were lower (P<0.01, P<0.05),and bone trabecula were more conspicuous in PTH and OSF-1 groups. The parameters of BMD, BV/TV and Tb.N in PTH group were higher than those in OSF-1 group (P<0.01), and TBPf was lower than that in OSF-1 group (P<0.01). Conclusion Subcutaneous injection of 80 μg/(kg·d) OSF-1 can increase bone mass and improve bone microstructure in ovariectomized rats.

Key words: Microcomputed tomography, Ovariectomized rats, Human osteoblast-stimulating factor, Postmenopausal osteoporosis

中图分类号: 

  • R589
[1] Lamprou M, Kaspiris A, Panagiotopoulos E, et al. The role of pleiotrophin in bone repair[J]. Injury, 2014, 45(12):1816-1823.
[2] Li G, Cui Y, McIlmurray L, et al. rhBMP-2, rhVEGF(165), rhPTN and thrombin-related peptide, TP508 induce chemotaxis of human osteoblasts and microvascular endothelial cells[J]. J Orthop Res, 2005, 23(3):680-685.
[3] Zhou HY, Ohnuma Y, Takita H, et al. Effects of a bone lysine-rich 18 kDa protein on osteoblast-like MC3T3-E1 cells[J]. Biochem Biophys Res Commun, 1992, 186(3):1288-1293.
[4] Bouderlique T, Henault E, Lebouvier A, et al. Pleiotrophin commits human bone marrow mesenchymal stromal cells towards hypertrophy during chondrogenesis[J]. PLoS One, 2014, 9(2):88287. doi: 10.1371/journal.pone.0088287.
[5] 康东红, 王燕, 张洪美, 等. OSF1在毕赤酵母中的分泌表达及其生物活性分析[J]. 生物工程学报, 2012, 28(1):1-9. KANG Donghong, WANG Yan, ZHANG Hongmei, et al. Expression and bioactivity of OSF-1 in Pichia pastoris [J]. Chin J Biotech, 2012, 28(1):1-9.
[6] 李素萍.骨质疏松动物模型的研究现状[J].中国组织工程研究与临床康复, 2011, 15(20):3767-3770.
[7] Milner PG, Li YS, Hoffman RM, et al. A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence[J]. Biochem Biophys Res Commun, 1989, 165(3):1096-1103.
[8] Deuel TF, Zhang N, Yeh HJ, et al. Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway[J]. Arch Biochem Biophys, 2002, 397(2):162-171.
[9] Xu C, Zhu S, Wu M, et al. Functional receptors and intracellular signal pathways of midkine (MK) and pleiotrophin (PTN) [J]. Biol Pharm Bull, 2014, 37(4):511-520.
[10] Himburg HA, Muramoto GG, Daher P, et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells [J]. Nat Med, 2010, 16(4):475-482.
[11] Kong Y, Bai PS, Nan KJ, et al. Pleiotrophin is a potential colorectal cancer prognostic factor that promotes VEGF expression and induces angiogenesis in colorectal cancer[J]. Int J Colorectal Dis, 2012, 27(3):287-298.
[12] Mikelis C, Koutsioumpa M, Papadimitriou E. Pleiotrophin as a possible new target for angiogenesis-related diseases and cancer[J]. Recent Pat Anticancer Drug Discov, 2007, 2(2):175-186.
[13] Herradón G, Pérez-García C. Targeting midkine and pleiotrophin signalling pathways in addiction and neurodegenerative disorders: recent progress and perspectives [J]. Br J Pharmacol, 2014, 171(4):837-848.
[14] Yao J, Hu XF, Feng XS, et al. Pleiotrophin promotes perineural invasion in pancreatic cancer [J]. World J Gastroenterol, 2013, 19(39):6555-6558.
[15] Masuda H, Tsujimura A, Yoshioka M, et al. Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1[J]. Biochem Biophys Res Commun, 1997, 238(2):528-533.
[16] Tare RS, Oreffo RO, Sato K, et al. Effects of targeted overexpression of pleiotrophin on postnatal bone development [J]. Biochem Biophys Res Commun, 2002, 298(3):324-332.
[17] Imai S, Heino TJ, Hienola A, et al. Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading[J]. Bone, 2009, 44(5):785-794.
[18] Petersen W, Wildemann B, Pufe T, et al. The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture healing: an immunohistochemical study in rats[J]. Arch Orthop Trauma Surg, 2004, 124(9):603-607.
[19] Li G, Bunn JR, Mushipe MT, et al. Effects of pleiotrophin (PTN) over-expression on mouse long bone development, fracture healing and bone repair[J]. Calcif Tissue Int, 2005, 76(4):299-306.
[20] Liedert A, Kassem M, Claes L, et al. Mechanosensitive promoter region in the human HB-GAM gene[J]. Biochem Biophys Res Commun, 2009, 387(2):289-293.
[21] Liedert A, Kaspar D, Claes L, et al. Signal transduction pathways involved in mechanical regulation of HB-GAM expression in osteoblastic cells[J]. Biochem Biophys Res Commun, 2006, 342(4):1070-1076.
[22] Albi E, Curcio F, Spelat R, et al. Loss of parafollicular cells during gravitational changes (microgravity, hypergravity) and the secret effect of pleiotrophin[J]. PLoS One, 2012, 7(12):48518. doi: 10.1371/journal.pone.0048518.
[23] McCarville JL, Clarke ST, Shastri P, et al. Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice[J]. PLoS One, 2013, 8(7):68961. doi: 10.1371/journal.pone.0068961.
[1] 宋轲,刘寰,武文亮,刘海春,李尚志,陈允震. 骨髓间充质干细胞、血小板凝胶和体外冲击波联合应用治疗骨不连[J]. 山东大学学报（医学版）, 2016, 54(6): 1-6.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发