Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.
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.
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Raul Hernandes
RH
Bortolin
Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Bento João
BJ
da Graça Azevedo Abreu
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Marcela
M
Abbott Galvão Ururahy
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Karla Simone
KS
Costa de Souza
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
João Felipe
JF
Bezerra
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Melina Bezerra
MB
Loureiro
Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Flávio Santos
FS
da Silva
Department of Morphology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Dáfiny Emanuele da Silva
DE
Marques
Department of Chemistry, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Angélica Amanda de Sousa
AA
Batista
Department of Chemistry, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Gisele
G
Oliveira
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
André Ducati
AD
Luchessi
Department of Pharmacy, State University of Paraiba, Campina Grande, Paraiba, Brazil.
Valéria Morgiana Gualberto Duarte Moreira
VM
Lima
Department of Pharmacy, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Carlos Eduardo Saraiva
CE
Miranda
Laboratory of Evaluation and Development of Biomaterials, Federal University of Campina Grande, Campina Grande, Paraiba, Brazil.
Marcus Vinicius
MV
Lia Fook
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Maria das Graças
Md
Almeida
Department of Chemistry, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Luciana Augusto
LA
de Rezende
Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
Adriana Augusto
AA
de Rezende
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000517:prevention & control*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000178:diet therapy / Q000235:genetics / Q000473:pathology; D019587:Dietary Supplements; D055119:Elastic Modulus; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000008:administration & dosage*
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D053244:Osteoprotegerin; D012333:RNA, Messenger; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin; D013311:Streptozocin; D020780:Matrix Metalloproteinase 9; D015032:Zinc