3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics
A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, th...
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| Veröffentlicht in: | International journal of molecular sciences 2021-03, Vol.22 (6), p.2925 |
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| description | A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings. |
| doi_str_mv | 10.3390/ijms22062925 |
| format | Article |
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In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22062925</identifier><identifier>PMID: 33805833</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alkaline Phosphatase - genetics ; Alkaline Phosphatase - metabolism ; Amputation ; Biomedical materials ; Bone and Bones - metabolism ; Bone and Bones - pathology ; Bone diseases ; Bone healing ; Bone Resorption - genetics ; Bone Resorption - metabolism ; Bone Resorption - pathology ; Bone turnover ; Calcification, Physiologic - genetics ; Carbonic Anhydrase II - genetics ; Carbonic Anhydrase II - metabolism ; Cathepsin K - genetics ; Cathepsin K - metabolism ; Cell Differentiation ; Cell Line, Tumor ; Coculture Techniques ; Collagen ; Deoxyribonucleic acid ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; DNA ; Drug screening ; Fractures ; Gene Expression Regulation ; Glucose ; Humans ; Insulin ; Metabolic Networks and Pathways - genetics ; Metabolism ; Mineralization ; Models, Biological ; Nonunion ; Osteoblasts ; Osteoblasts - metabolism ; Osteoblasts - pathology ; Osteoclasts ; Osteoclasts - metabolism ; Osteoclasts - pathology ; Osteoprotegerin - genetics ; Osteoprotegerin - metabolism ; RANK Ligand - genetics ; RANK Ligand - metabolism ; Risk analysis ; Risk factors ; Stability ; Tartrate-Resistant Acid Phosphatase - genetics ; Tartrate-Resistant Acid Phosphatase - metabolism ; THP-1 Cells ; Tissue engineering ; Tissue Scaffolds</subject><ispartof>International journal of molecular sciences, 2021-03, Vol.22 (6), p.2925</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-e729c8cd067008d76e1c46f0b32bfa78eedf613447c0e33634c4b0140b13a6423</citedby><cites>FETCH-LOGICAL-c412t-e729c8cd067008d76e1c46f0b32bfa78eedf613447c0e33634c4b0140b13a6423</cites><orcidid>0000-0002-9311-0131 ; 0000-0002-5160-2111 ; 0000-0003-4347-1702 ; 0000-0002-6666-6791</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002142/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002142/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33805833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Häussling, Victor</creatorcontrib><creatorcontrib>Aspera-Werz, Romina H</creatorcontrib><creatorcontrib>Rinderknecht, Helen</creatorcontrib><creatorcontrib>Springer, Fabian</creatorcontrib><creatorcontrib>Arnscheidt, Christian</creatorcontrib><creatorcontrib>Menger, Maximilian M</creatorcontrib><creatorcontrib>Histing, Tina</creatorcontrib><creatorcontrib>Nussler, Andreas K</creatorcontrib><creatorcontrib>Ehnert, Sabrina</creatorcontrib><title>3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings.</description><subject>Alkaline Phosphatase - genetics</subject><subject>Alkaline Phosphatase - metabolism</subject><subject>Amputation</subject><subject>Biomedical materials</subject><subject>Bone and Bones - metabolism</subject><subject>Bone and Bones - pathology</subject><subject>Bone diseases</subject><subject>Bone healing</subject><subject>Bone Resorption - genetics</subject><subject>Bone Resorption - metabolism</subject><subject>Bone Resorption - pathology</subject><subject>Bone turnover</subject><subject>Calcification, Physiologic - genetics</subject><subject>Carbonic Anhydrase II - genetics</subject><subject>Carbonic Anhydrase II - metabolism</subject><subject>Cathepsin K - genetics</subject><subject>Cathepsin K - metabolism</subject><subject>Cell Differentiation</subject><subject>Cell Line, Tumor</subject><subject>Coculture Techniques</subject><subject>Collagen</subject><subject>Deoxyribonucleic acid</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - 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genetics</topic><topic>Metabolism</topic><topic>Mineralization</topic><topic>Models, Biological</topic><topic>Nonunion</topic><topic>Osteoblasts</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoblasts - pathology</topic><topic>Osteoclasts</topic><topic>Osteoclasts - metabolism</topic><topic>Osteoclasts - pathology</topic><topic>Osteoprotegerin - genetics</topic><topic>Osteoprotegerin - metabolism</topic><topic>RANK Ligand - genetics</topic><topic>RANK Ligand - metabolism</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Stability</topic><topic>Tartrate-Resistant Acid Phosphatase - genetics</topic><topic>Tartrate-Resistant Acid Phosphatase - metabolism</topic><topic>THP-1 Cells</topic><topic>Tissue engineering</topic><topic>Tissue Scaffolds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Häussling, Victor</creatorcontrib><creatorcontrib>Aspera-Werz, Romina H</creatorcontrib><creatorcontrib>Rinderknecht, Helen</creatorcontrib><creatorcontrib>Springer, Fabian</creatorcontrib><creatorcontrib>Arnscheidt, Christian</creatorcontrib><creatorcontrib>Menger, Maximilian M</creatorcontrib><creatorcontrib>Histing, Tina</creatorcontrib><creatorcontrib>Nussler, Andreas K</creatorcontrib><creatorcontrib>Ehnert, Sabrina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Häussling, Victor</au><au>Aspera-Werz, Romina H</au><au>Rinderknecht, Helen</au><au>Springer, Fabian</au><au>Arnscheidt, Christian</au><au>Menger, Maximilian M</au><au>Histing, Tina</au><au>Nussler, Andreas K</au><au>Ehnert, Sabrina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2021-03-13</date><risdate>2021</risdate><volume>22</volume><issue>6</issue><spage>2925</spage><pages>2925-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33805833</pmid><doi>10.3390/ijms22062925</doi><orcidid>https://orcid.org/0000-0002-9311-0131</orcidid><orcidid>https://orcid.org/0000-0002-5160-2111</orcidid><orcidid>https://orcid.org/0000-0003-4347-1702</orcidid><orcidid>https://orcid.org/0000-0002-6666-6791</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2021-03, Vol.22 (6), p.2925 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Alkaline Phosphatase - genetics Alkaline Phosphatase - metabolism Amputation Biomedical materials Bone and Bones - metabolism Bone and Bones - pathology Bone diseases Bone healing Bone Resorption - genetics Bone Resorption - metabolism Bone Resorption - pathology Bone turnover Calcification, Physiologic - genetics Carbonic Anhydrase II - genetics Carbonic Anhydrase II - metabolism Cathepsin K - genetics Cathepsin K - metabolism Cell Differentiation Cell Line, Tumor Coculture Techniques Collagen Deoxyribonucleic acid Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - pathology DNA Drug screening Fractures Gene Expression Regulation Glucose Humans Insulin Metabolic Networks and Pathways - genetics Metabolism Mineralization Models, Biological Nonunion Osteoblasts Osteoblasts - metabolism Osteoblasts - pathology Osteoclasts Osteoclasts - metabolism Osteoclasts - pathology Osteoprotegerin - genetics Osteoprotegerin - metabolism RANK Ligand - genetics RANK Ligand - metabolism Risk analysis Risk factors Stability Tartrate-Resistant Acid Phosphatase - genetics Tartrate-Resistant Acid Phosphatase - metabolism THP-1 Cells Tissue engineering Tissue Scaffolds |
| title | 3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics |
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