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 effec...
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0125349 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0125349</identifier><identifier>PMID: 25933189</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biochemical analysis ; Biocompatibility ; Biomechanical engineering ; Biomechanical Phenomena ; Biomechanics ; Biomedical materials ; Bone density ; Bone Density - drug effects ; Bone growth ; Bone loss ; Bone Resorption - prevention & control ; Bone strength ; Bone turnover ; Chronic illnesses ; Collagen ; Collagen (type I) ; Collagen Type I - genetics ; Collagen Type I - metabolism ; Diabetes ; Diabetes mellitus ; 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 ; Diabetes therapy ; Dietary Supplements ; Elastic Modulus ; Femur ; Femur - drug effects ; Femur - metabolism ; Femur - pathology ; Gelatinase B ; Gene expression ; Gene Expression Regulation ; Genes ; Growth factors ; Humans ; Hyperglycemia ; Male ; Matrix Metalloproteinase 9 - genetics ; Matrix Metalloproteinase 9 - metabolism ; Mechanical properties ; Metabolism ; Modulus of elasticity ; Morphology ; Osteoblastogenesis ; Osteocalcin - genetics ; Osteocalcin - metabolism ; Osteogenesis ; Osteoporosis ; Osteoprotegerin ; Osteoprotegerin - genetics ; Osteoprotegerin - metabolism ; Pharmacy ; Phosphatase ; Physiological aspects ; Rats ; Rats, Wistar ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Stiffness ; Streptozocin ; Studies ; Supplements ; Tibia ; Tibia - drug effects ; Tibia - metabolism ; Tibia - pathology ; Type 1 diabetes ; Zinc ; Zinc (Nutrient) ; Zinc - administration & dosage</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0125349</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Bortolin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Bortolin et al 2015 Bortolin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-935e6d0d0f3de4cd861fb6234a81442363993e5ad4318a71e784bbebb2c5b8cc3</citedby><cites>FETCH-LOGICAL-c692t-935e6d0d0f3de4cd861fb6234a81442363993e5ad4318a71e784bbebb2c5b8cc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416905/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416905/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25933189$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bortolin, Raul Hernandes</creatorcontrib><creatorcontrib>da Graça Azevedo Abreu, Bento João</creatorcontrib><creatorcontrib>Abbott Galvão Ururahy, Marcela</creatorcontrib><creatorcontrib>Costa de Souza, Karla Simone</creatorcontrib><creatorcontrib>Bezerra, João Felipe</creatorcontrib><creatorcontrib>Loureiro, Melina Bezerra</creatorcontrib><creatorcontrib>da Silva, Flávio Santos</creatorcontrib><creatorcontrib>Marques, Dáfiny Emanuele da Silva</creatorcontrib><creatorcontrib>Batista, Angélica Amanda de Sousa</creatorcontrib><creatorcontrib>Oliveira, Gisele</creatorcontrib><creatorcontrib>Luchessi, André Ducati</creatorcontrib><creatorcontrib>Lima, Valéria Morgiana Gualberto Duarte Moreira</creatorcontrib><creatorcontrib>Miranda, Carlos Eduardo Saraiva</creatorcontrib><creatorcontrib>Lia Fook, Marcus Vinicius</creatorcontrib><creatorcontrib>Almeida, Maria das Graças</creatorcontrib><creatorcontrib>de Rezende, Luciana Augusto</creatorcontrib><creatorcontrib>de Rezende, Adriana Augusto</creatorcontrib><title>Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Animals</subject><subject>Biochemical analysis</subject><subject>Biocompatibility</subject><subject>Biomechanical engineering</subject><subject>Biomechanical Phenomena</subject><subject>Biomechanics</subject><subject>Biomedical materials</subject><subject>Bone density</subject><subject>Bone Density - drug effects</subject><subject>Bone growth</subject><subject>Bone loss</subject><subject>Bone Resorption - prevention & control</subject><subject>Bone strength</subject><subject>Bone turnover</subject><subject>Chronic illnesses</subject><subject>Collagen</subject><subject>Collagen (type I)</subject><subject>Collagen Type I - genetics</subject><subject>Collagen Type I - metabolism</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - chemically induced</subject><subject>Diabetes Mellitus, Experimental - diet therapy</subject><subject>Diabetes Mellitus, Experimental - genetics</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetes Mellitus, Type 1 - diet therapy</subject><subject>Diabetes Mellitus, Type 1 - genetics</subject><subject>Diabetes Mellitus, Type 1 - pathology</subject><subject>Diabetes therapy</subject><subject>Dietary Supplements</subject><subject>Elastic Modulus</subject><subject>Femur</subject><subject>Femur - drug effects</subject><subject>Femur - metabolism</subject><subject>Femur - pathology</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hyperglycemia</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Mechanical properties</subject><subject>Metabolism</subject><subject>Modulus of elasticity</subject><subject>Morphology</subject><subject>Osteoblastogenesis</subject><subject>Osteocalcin - genetics</subject><subject>Osteocalcin - metabolism</subject><subject>Osteogenesis</subject><subject>Osteoporosis</subject><subject>Osteoprotegerin</subject><subject>Osteoprotegerin - genetics</subject><subject>Osteoprotegerin - metabolism</subject><subject>Pharmacy</subject><subject>Phosphatase</subject><subject>Physiological aspects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Stiffness</subject><subject>Streptozocin</subject><subject>Studies</subject><subject>Supplements</subject><subject>Tibia</subject><subject>Tibia - drug effects</subject><subject>Tibia - metabolism</subject><subject>Tibia - pathology</subject><subject>Type 1 diabetes</subject><subject>Zinc</subject><subject>Zinc (Nutrient)</subject><subject>Zinc - administration & 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against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-935e6d0d0f3de4cd861fb6234a81442363993e5ad4318a71e784bbebb2c5b8cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Biochemical analysis</topic><topic>Biocompatibility</topic><topic>Biomechanical engineering</topic><topic>Biomechanical Phenomena</topic><topic>Biomechanics</topic><topic>Biomedical materials</topic><topic>Bone density</topic><topic>Bone Density - drug effects</topic><topic>Bone growth</topic><topic>Bone loss</topic><topic>Bone Resorption - prevention & control</topic><topic>Bone strength</topic><topic>Bone turnover</topic><topic>Chronic illnesses</topic><topic>Collagen</topic><topic>Collagen (type I)</topic><topic>Collagen Type I - genetics</topic><topic>Collagen Type I - metabolism</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - chemically induced</topic><topic>Diabetes Mellitus, Experimental - diet therapy</topic><topic>Diabetes Mellitus, Experimental - genetics</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetes Mellitus, Type 1 - diet therapy</topic><topic>Diabetes Mellitus, Type 1 - genetics</topic><topic>Diabetes Mellitus, Type 1 - pathology</topic><topic>Diabetes therapy</topic><topic>Dietary Supplements</topic><topic>Elastic Modulus</topic><topic>Femur</topic><topic>Femur - drug effects</topic><topic>Femur - metabolism</topic><topic>Femur - pathology</topic><topic>Gelatinase B</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hyperglycemia</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Mechanical properties</topic><topic>Metabolism</topic><topic>Modulus of elasticity</topic><topic>Morphology</topic><topic>Osteoblastogenesis</topic><topic>Osteocalcin - genetics</topic><topic>Osteocalcin - metabolism</topic><topic>Osteogenesis</topic><topic>Osteoporosis</topic><topic>Osteoprotegerin</topic><topic>Osteoprotegerin - genetics</topic><topic>Osteoprotegerin - metabolism</topic><topic>Pharmacy</topic><topic>Phosphatase</topic><topic>Physiological aspects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Stiffness</topic><topic>Streptozocin</topic><topic>Studies</topic><topic>Supplements</topic><topic>Tibia</topic><topic>Tibia - drug effects</topic><topic>Tibia - metabolism</topic><topic>Tibia - pathology</topic><topic>Type 1 diabetes</topic><topic>Zinc</topic><topic>Zinc (Nutrient)</topic><topic>Zinc - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bortolin, Raul Hernandes</creatorcontrib><creatorcontrib>da Graça Azevedo Abreu, Bento João</creatorcontrib><creatorcontrib>Abbott Galvão Ururahy, Marcela</creatorcontrib><creatorcontrib>Costa de Souza, Karla Simone</creatorcontrib><creatorcontrib>Bezerra, João Felipe</creatorcontrib><creatorcontrib>Loureiro, Melina Bezerra</creatorcontrib><creatorcontrib>da Silva, Flávio Santos</creatorcontrib><creatorcontrib>Marques, Dáfiny Emanuele da Silva</creatorcontrib><creatorcontrib>Batista, Angélica Amanda de Sousa</creatorcontrib><creatorcontrib>Oliveira, Gisele</creatorcontrib><creatorcontrib>Luchessi, André Ducati</creatorcontrib><creatorcontrib>Lima, Valéria Morgiana Gualberto Duarte Moreira</creatorcontrib><creatorcontrib>Miranda, Carlos Eduardo Saraiva</creatorcontrib><creatorcontrib>Lia Fook, Marcus Vinicius</creatorcontrib><creatorcontrib>Almeida, Maria das Graças</creatorcontrib><creatorcontrib>de Rezende, Luciana Augusto</creatorcontrib><creatorcontrib>de Rezende, Adriana Augusto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health 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(ProQuest)</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bortolin, Raul Hernandes</au><au>da Graça Azevedo Abreu, Bento João</au><au>Abbott Galvão Ururahy, Marcela</au><au>Costa de Souza, Karla Simone</au><au>Bezerra, João Felipe</au><au>Loureiro, Melina Bezerra</au><au>da Silva, Flávio Santos</au><au>Marques, Dáfiny Emanuele da Silva</au><au>Batista, Angélica Amanda de Sousa</au><au>Oliveira, Gisele</au><au>Luchessi, André Ducati</au><au>Lima, Valéria Morgiana Gualberto Duarte Moreira</au><au>Miranda, Carlos Eduardo Saraiva</au><au>Lia Fook, Marcus Vinicius</au><au>Almeida, Maria das Graças</au><au>de Rezende, Luciana Augusto</au><au>de Rezende, Adriana Augusto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0125349</spage><pages>e0125349-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25933189</pmid><doi>10.1371/journal.pone.0125349</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0125349 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1677644934 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Biochemical analysis Biocompatibility Biomechanical engineering Biomechanical Phenomena Biomechanics Biomedical materials Bone density Bone Density - drug effects Bone growth Bone loss Bone Resorption - prevention & control Bone strength Bone turnover Chronic illnesses Collagen Collagen (type I) Collagen Type I - genetics Collagen Type I - metabolism Diabetes Diabetes mellitus 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 Diabetes therapy Dietary Supplements Elastic Modulus Femur Femur - drug effects Femur - metabolism Femur - pathology Gelatinase B Gene expression Gene Expression Regulation Genes Growth factors Humans Hyperglycemia Male Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Mechanical properties Metabolism Modulus of elasticity Morphology Osteoblastogenesis Osteocalcin - genetics Osteocalcin - metabolism Osteogenesis Osteoporosis Osteoprotegerin Osteoprotegerin - genetics Osteoprotegerin - metabolism Pharmacy Phosphatase Physiological aspects Rats Rats, Wistar RNA RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Stiffness Streptozocin Studies Supplements Tibia Tibia - drug effects Tibia - metabolism Tibia - pathology Type 1 diabetes Zinc Zinc (Nutrient) Zinc - administration & dosage |
| title | Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T08%3A24%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Protection%20against%20T1DM-Induced%20Bone%20Loss%20by%20Zinc%20Supplementation:%20Biomechanical,%20Histomorphometric,%20and%20Molecular%20Analyses%20in%20STZ-Induced%20Diabetic%20Rats&rft.jtitle=PloS%20one&rft.au=Bortolin,%20Raul%20Hernandes&rft.date=2015-05-01&rft.volume=10&rft.issue=5&rft.spage=e0125349&rft.pages=e0125349-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0125349&rft_dat=%3Cgale_plos_%3EA423835703%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1677644934&rft_id=info:pmid/25933189&rft_galeid=A423835703&rft_doaj_id=oai_doaj_org_article_2cff49fb1286444797f166822edd159b&rfr_iscdi=true |