Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats

PLoS One. 2015 May 1;10(5):e0125349. doi: 10.1371/journal.pone.0125349. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone Density / drug effects*
  • Bone Resorption / prevention & control*
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / diet therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / diet therapy
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / pathology
  • Dietary Supplements*
  • Elastic Modulus
  • Femur / drug effects
  • Femur / metabolism
  • Femur / pathology
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Tibia / drug effects
  • Tibia / metabolism
  • Tibia / pathology
  • Zinc / administration & dosage*

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Osteoprotegerin
  • RNA, Messenger
  • Tnfrsf11b protein, rat
  • Osteocalcin
  • Streptozocin
  • Matrix Metalloproteinase 9
  • Zinc

Grants and funding

BJGAA received financial support by National Council of scientific and technological development (protocol 475801/2010). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.