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维甲酸受体选择性激活对大鼠骨代谢和骨力学性能的负面影响。

The Negative Impact of Selective Activation of Retinoic Acid Receptors on Bone Metabolism and Bone Mechanical Properties in Rats.

作者信息

Nowak Beata, Matuszewska Agnieszka, Filipiak Jarosław, Nikodem Anna, Merwid-Ląd Anna, Pieśniewska Małgorzata, Kwiatkowska Joanna, Grotthus Bartosz, Szeląg Adam

机构信息

Department of Pharmacology, Wroclaw Medical University, Poland.

Division of Biomedical Engineering and Experimental Mechanics, Wroclaw University of Technology, Poland.

出版信息

Adv Clin Exp Med. 2016 Mar-Apr;25(2):213-8. doi: 10.17219/acem/41860.

Abstract

BACKGROUND

Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Data from several studies concerning the influence of retinol on bone homeostasis are inconsistent.

OBJECTIVES

The purpose of this study was to investigate the influence of tazarotene, a selective agonist of the retinoic acid receptor (RAR), on bone metabolism and bone mechanical properties in rats.

MATERIAL AND METHODS

Sixteen male Wistar rats were assigned either to the group receiving tazarotene or to the control group. Serum biochemical markers of bone turnover (osteocalcin: OC, tartrate resistant acid phosphatase 5: TRACP5b, and osteoprotegerin: OPG) and the mechanical properties of bones were analyzed.

RESULTS

The mean Young's modulus was 24% higher (p < 0.05) in the control group than in the group receiving tazarotene. The stiffness of femur bones was 25% lower (p < 0.05) in rats receiving tazarotene. Flexural yield stress was slightly (2%) decreased in the tazarotene group, but the difference was not statistically significant. In the tazarotene group significantly lower serum concentration of bone turnover markers were obeserved (TRACP5b: 0.86 ± 0.30 ng/mL vs. 2.17 ± 0.67 ng/mL, OC: 7.77 ± 2.28 ng/mL vs. 13.04 ± 3.54 ng/mL and OPG: 0.09 ± 0.04 ng/mL vs. 0.27 ± 0.10) than in the control group.

CONCLUSIONS

Tazarotene worsened bone mechanical properties and inhibited bone turnover in rats. These results suggest that tazarotene has a negative impact on bone metabolism and that it exerts osteoporotic activity.

摘要

背景

药物性骨质疏松是一个重大的健康问题,因为许多药物对骨代谢有有害影响。几项关于视黄醇对骨稳态影响的研究数据并不一致。

目的

本研究旨在探讨维甲酸受体(RAR)选择性激动剂他扎罗汀对大鼠骨代谢和骨力学性能的影响。

材料与方法

将16只雄性Wistar大鼠分为接受他扎罗汀的组和对照组。分析骨转换的血清生化标志物(骨钙素:OC、抗酒石酸酸性磷酸酶5:TRACP5b和骨保护素:OPG)以及骨的力学性能。

结果

对照组的平均杨氏模量比接受他扎罗汀的组高24%(p<0.05)。接受他扎罗汀的大鼠股骨刚度低25%(p<0.05)。他扎罗汀组的弯曲屈服应力略有下降(2%),但差异无统计学意义。他扎罗汀组的骨转换标志物血清浓度显著低于对照组(TRACP5b:0.86±0.30 ng/mL对2.17±0.67 ng/mL,OC:7.77±2.28 ng/mL对13.04±3.54 ng/mL,OPG:0.09±0.04 ng/mL对0.27±0.10)。

结论

他扎罗汀使大鼠的骨力学性能恶化并抑制骨转换。这些结果表明他扎罗汀对骨代谢有负面影响,并具有骨质疏松活性。

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