Bortolin Raul Hernandes, da Graça Azevedo Abreu Bento João, Abbott Galvão Ururahy Marcela, Costa de Souza Karla Simone, Bezerra João Felipe, Loureiro Melina Bezerra, da Silva Flávio Santos, Marques Dáfiny Emanuele da Silva, Batista Angélica Amanda de Sousa, Oliveira Gisele, Luchessi André Ducati, Lima Valéria Morgiana Gualberto Duarte Moreira, Miranda Carlos Eduardo Saraiva, Lia Fook Marcus Vinicius, Almeida Maria das Graças, de Rezende Luciana Augusto, de Rezende Adriana Augusto
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
PLoS One. 2015 May 1;10(5):e0125349. doi: 10.1371/journal.pone.0125349. eCollection 2015.
Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days) type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM), and T1DM plus zinc supplementation (T1DMS). Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus), and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic and protective effect of zinc under chronic diabetic conditions. Furthermore, these results indicate that zinc supplementation could act as a complementary therapy in chronic T1DM.
多项研究已证实糖尿病与骨代谢改变之间存在关联；然而，其潜在机制尚未完全明确。尽管锌被认为是预防糖尿病所致骨质流失的潜在药物，但尚无证据表明其在慢性糖尿病状态下的作用。本研究评估了在慢性（90天）1型糖尿病诱导的骨质流失模型中补充锌的效果。雄性Wistar大鼠分为三组：对照组、1型糖尿病（T1DM）组和T1DM加锌补充组（T1DMS）。评估了血清生化分析、胫骨组织形态计量学、生物力学和胶原蛋白含量分析以及股骨mRNA表达。与T1DM组相比，补充锌的组显示出组织形态计量学参数增加，如骨小梁宽度（TbWi）和骨面积比（BAr），骨小梁间距（TbSp）减小，生物力学参数增加（最大载荷、刚度、极限应变和杨氏模量），以及I型胶原蛋白含量增加。有趣的是，T1DMS组和对照组之间观察到这些参数的相似值。这些结果证明了锌对维持骨骼强度和柔韧性的保护作用。此外，在T1DMS组中观察到骨保护素（OPG）、I型胶原蛋白（COL1A）和基质金属蛋白酶-9（MMP-9）基因的下调，锌的合成代谢作用通过骨钙素（OC）表达增加和血清碱性磷酸酶（ALP）活性增加得到证实，两者均与成骨细胞生成有关，表明对骨形成有积极作用。相比之下，T1DM组显示出过度的骨质流失，通过组织形态计量学和生物力学参数降低观察到，这是糖尿病相关骨质流失的特征。通过OPG、COL1A和MMP-9基因的上调也观察到了骨质流失。总之，锌对维持骨骼结构和生物力学参数有积极作用。事实上，即使在慢性高血糖情况下，OC上调以及对OPG、COL1A和MMP-9 mRNA表达的控制，都支持锌在慢性糖尿病状态下的合成代谢和保护作用。此外，这些结果表明补充锌可作为慢性1型糖尿病的辅助治疗方法。
