Nutrient-Dependent Mitochondrial Fission Enhances Osteoblast Function
The bone synthesizing function of osteoblasts (OBs) is a highly demanding energy process that requires nutrients. However, how nutrient availability affects OBs behavior and bone mineralization remain to be fully understood. MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiol...
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| Veröffentlicht in: | Nutrients 2023-05, Vol.15 (9), p.2222 |
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| creator | Menale, Ciro Trinchese, Giovanna Aiello, Immacolata Scalia, Giulia Dentice, Monica Mollica, Maria Pina Yoon, Nal Ae Diano, Sabrina |
| description | The bone synthesizing function of osteoblasts (OBs) is a highly demanding energy process that requires nutrients. However, how nutrient availability affects OBs behavior and bone mineralization remain to be fully understood.
MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiological levels of glucose (G; 5.5 mM) alone or with the addition of palmitic acid (G+PA) at different concentrations. Mitochondria morphology and activity were evaluated by fluorescence microscopy, qPCR, and oxygen consumption rate (OCR) measurement, and OBs function was assessed by mineralization assay.
The addition of non-lipotoxic levels of 25 μM PA to G increased mineralization in OBs. G+25 μM PA exposure reduced mitochondria size in OBs, which was associated with increased activation of dynamin-related protein 1, a mitochondrial fission protein, enhanced mitochondria OCR and ATP production, and increased expression of oxidative phosphorylation genes. Treatment with Mdivi-1, a putative inhibitor of mitochondrial fission, reduced osteogenesis and mitochondrial respiration in OBs.
Our results revealed that OBs function was enhanced in the presence of glucose and PA at 25 μM. This was associated with increased OBs mitochondrial respiration and dynamics. These results suggest a role for nutrient availability in bone physiology and pathophysiology. |
| doi_str_mv | 10.3390/nu15092222 |
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MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiological levels of glucose (G; 5.5 mM) alone or with the addition of palmitic acid (G+PA) at different concentrations. Mitochondria morphology and activity were evaluated by fluorescence microscopy, qPCR, and oxygen consumption rate (OCR) measurement, and OBs function was assessed by mineralization assay.
The addition of non-lipotoxic levels of 25 μM PA to G increased mineralization in OBs. G+25 μM PA exposure reduced mitochondria size in OBs, which was associated with increased activation of dynamin-related protein 1, a mitochondrial fission protein, enhanced mitochondria OCR and ATP production, and increased expression of oxidative phosphorylation genes. Treatment with Mdivi-1, a putative inhibitor of mitochondrial fission, reduced osteogenesis and mitochondrial respiration in OBs.
Our results revealed that OBs function was enhanced in the presence of glucose and PA at 25 μM. This was associated with increased OBs mitochondrial respiration and dynamics. These results suggest a role for nutrient availability in bone physiology and pathophysiology.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu15092222</identifier><identifier>PMID: 37432387</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Amino acids ; Autophagy ; Availability ; Cell culture ; Cell growth ; Cytotoxicity ; Dynamin ; Electron transport ; Ethylenediaminetetraacetic acid ; Experiments ; Fatty acids ; Flow cytometry ; Fluorescence ; Fluorescence microscopy ; Gene expression ; Genes ; Glucose ; Glucose - pharmacology ; Homeostasis ; Lipids ; Metabolism ; Mineralization ; Mitochondria ; Mitochondrial Dynamics ; Mitochondrial Proteins ; Nutrient availability ; Nutrient dynamics ; Nutrients ; Osteoblasts ; Osteogenesis ; Oxidation ; Oxidative phosphorylation ; Oxygen consumption ; Palmitic acid ; Phosphatase ; Phosphorylation ; Physiology ; Proteins ; Respiration ; Saturated fatty acids</subject><ispartof>Nutrients, 2023-05, Vol.15 (9), p.2222</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-b91bc8e8dfb9bf692d2249a5e87ff89582be541b963a9f5b612d1567c2790af73</citedby><cites>FETCH-LOGICAL-c474t-b91bc8e8dfb9bf692d2249a5e87ff89582be541b963a9f5b612d1567c2790af73</cites><orcidid>0009-0000-6724-2547 ; 0000-0002-9977-3761 ; 0000-0002-4096-6876 ; 0000-0001-5782-2089</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/PMC10181360/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181360/$$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/37432387$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Menale, Ciro</creatorcontrib><creatorcontrib>Trinchese, Giovanna</creatorcontrib><creatorcontrib>Aiello, Immacolata</creatorcontrib><creatorcontrib>Scalia, Giulia</creatorcontrib><creatorcontrib>Dentice, Monica</creatorcontrib><creatorcontrib>Mollica, Maria Pina</creatorcontrib><creatorcontrib>Yoon, Nal Ae</creatorcontrib><creatorcontrib>Diano, Sabrina</creatorcontrib><title>Nutrient-Dependent Mitochondrial Fission Enhances Osteoblast Function</title><title>Nutrients</title><addtitle>Nutrients</addtitle><description>The bone synthesizing function of osteoblasts (OBs) is a highly demanding energy process that requires nutrients. However, how nutrient availability affects OBs behavior and bone mineralization remain to be fully understood.
MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiological levels of glucose (G; 5.5 mM) alone or with the addition of palmitic acid (G+PA) at different concentrations. Mitochondria morphology and activity were evaluated by fluorescence microscopy, qPCR, and oxygen consumption rate (OCR) measurement, and OBs function was assessed by mineralization assay.
The addition of non-lipotoxic levels of 25 μM PA to G increased mineralization in OBs. G+25 μM PA exposure reduced mitochondria size in OBs, which was associated with increased activation of dynamin-related protein 1, a mitochondrial fission protein, enhanced mitochondria OCR and ATP production, and increased expression of oxidative phosphorylation genes. Treatment with Mdivi-1, a putative inhibitor of mitochondrial fission, reduced osteogenesis and mitochondrial respiration in OBs.
Our results revealed that OBs function was enhanced in the presence of glucose and PA at 25 μM. This was associated with increased OBs mitochondrial respiration and dynamics. These results suggest a role for nutrient availability in bone physiology and pathophysiology.</description><subject>Amino acids</subject><subject>Autophagy</subject><subject>Availability</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cytotoxicity</subject><subject>Dynamin</subject><subject>Electron transport</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Experiments</subject><subject>Fatty acids</subject><subject>Flow cytometry</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Glucose</subject><subject>Glucose - pharmacology</subject><subject>Homeostasis</subject><subject>Lipids</subject><subject>Metabolism</subject><subject>Mineralization</subject><subject>Mitochondria</subject><subject>Mitochondrial Dynamics</subject><subject>Mitochondrial Proteins</subject><subject>Nutrient availability</subject><subject>Nutrient dynamics</subject><subject>Nutrients</subject><subject>Osteoblasts</subject><subject>Osteogenesis</subject><subject>Oxidation</subject><subject>Oxidative phosphorylation</subject><subject>Oxygen consumption</subject><subject>Palmitic acid</subject><subject>Phosphatase</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Respiration</subject><subject>Saturated fatty acids</subject><issn>2072-6643</issn><issn>2072-6643</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkU1PGzEQhq2qCFDKhR9QrdRLVWmpP3bt9QmhkLSV-Li0Z8v2jonRxk7tXST-fR0RCKCODx55nnnHM4PQKcFnjEn8PUykxZIW-4COKRa05rxhH1_5R-gk53u8NYEFZ4foiImGUdaJY7S4mcbkIYz1JWwg9MWrrv0Y7SqGPnk9VEufs4-hWoSVDhZydZtHiGbQeayWU7BjCX5CB04PGU529wz9WS5-z3_WV7c_fs0vrmrbiGasjSTGdtD1zkjjuKQ9pY3ULXTCuU62HTXQNsRIzrR0reGE9qTlwlIhsXaCzdD5k-5mMmvobflt0oPaJL_W6VFF7dXbSPArdRcfFMGkI4zjovB1p5Di3wnyqNY-WxgGHSBOWdGOcSoFK3OboS_v0Ps4pVD6KxShnMgC76k7PYDywcVS2G5F1YVoJGWsEduyZ_-hyulh7W0M4Hx5f5Pw7SnBpphzAvfSJMFqu3i1X3yBP78eywv6vGb2D9UBpv4</recordid><startdate>20230508</startdate><enddate>20230508</enddate><creator>Menale, Ciro</creator><creator>Trinchese, Giovanna</creator><creator>Aiello, Immacolata</creator><creator>Scalia, Giulia</creator><creator>Dentice, Monica</creator><creator>Mollica, Maria Pina</creator><creator>Yoon, Nal Ae</creator><creator>Diano, Sabrina</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0009-0000-6724-2547</orcidid><orcidid>https://orcid.org/0000-0002-9977-3761</orcidid><orcidid>https://orcid.org/0000-0002-4096-6876</orcidid><orcidid>https://orcid.org/0000-0001-5782-2089</orcidid></search><sort><creationdate>20230508</creationdate><title>Nutrient-Dependent Mitochondrial Fission Enhances Osteoblast Function</title><author>Menale, Ciro ; 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However, how nutrient availability affects OBs behavior and bone mineralization remain to be fully understood.
MC3T3-E1 cell line and primary OBs (OBs) cultures were treated with physiological levels of glucose (G; 5.5 mM) alone or with the addition of palmitic acid (G+PA) at different concentrations. Mitochondria morphology and activity were evaluated by fluorescence microscopy, qPCR, and oxygen consumption rate (OCR) measurement, and OBs function was assessed by mineralization assay.
The addition of non-lipotoxic levels of 25 μM PA to G increased mineralization in OBs. G+25 μM PA exposure reduced mitochondria size in OBs, which was associated with increased activation of dynamin-related protein 1, a mitochondrial fission protein, enhanced mitochondria OCR and ATP production, and increased expression of oxidative phosphorylation genes. Treatment with Mdivi-1, a putative inhibitor of mitochondrial fission, reduced osteogenesis and mitochondrial respiration in OBs.
Our results revealed that OBs function was enhanced in the presence of glucose and PA at 25 μM. This was associated with increased OBs mitochondrial respiration and dynamics. These results suggest a role for nutrient availability in bone physiology and pathophysiology.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>37432387</pmid><doi>10.3390/nu15092222</doi><orcidid>https://orcid.org/0009-0000-6724-2547</orcidid><orcidid>https://orcid.org/0000-0002-9977-3761</orcidid><orcidid>https://orcid.org/0000-0002-4096-6876</orcidid><orcidid>https://orcid.org/0000-0001-5782-2089</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acids Autophagy Availability Cell culture Cell growth Cytotoxicity Dynamin Electron transport Ethylenediaminetetraacetic acid Experiments Fatty acids Flow cytometry Fluorescence Fluorescence microscopy Gene expression Genes Glucose Glucose - pharmacology Homeostasis Lipids Metabolism Mineralization Mitochondria Mitochondrial Dynamics Mitochondrial Proteins Nutrient availability Nutrient dynamics Nutrients Osteoblasts Osteogenesis Oxidation Oxidative phosphorylation Oxygen consumption Palmitic acid Phosphatase Phosphorylation Physiology Proteins Respiration Saturated fatty acids |
| title | Nutrient-Dependent Mitochondrial Fission Enhances Osteoblast Function |
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