Matrix Biology Plus最新文献

{"title":"A human stem cell-derived model reveals pathologic extracellular matrix remodeling in diabetic podocyte injury","authors":"Yasmin Roye ,&nbsp;Carmen Miller ,&nbsp;Titilola D. Kalejaiye ,&nbsp;Samira Musah","doi":"10.1016/j.mbplus.2024.100164","DOIUrl":"10.1016/j.mbplus.2024.100164","url":null,"abstract":"<div><div>Diabetic nephropathy results from chronic (or uncontrolled) hyperglycemia and is the leading cause of kidney failure. The kidney’s glomerular podocytes are highly susceptible to diabetic injury and subsequent non-reversible degeneration. We generated a human induced pluripotent stem (iPS) cell-derived model of diabetic podocytopathy to investigate disease pathogenesis and progression. The model recapitulated hallmarks of podocytopathy that precede proteinuria including retraction of foot processes and podocytopenia (detachment from the extracellular matrix (ECM)). Moreover, hyperglycemia-induced injury to podocytes exacerbated remodeling of the ECM. Specifically, mature podocytes aberrantly increased expression and excessively deposited collagen (IV)α1α1α2 that is normally abundant in the embryonic glomerulus. This collagen (IV) imbalance coincided with dysregulation of lineage-specific proteins, structural abnormalities of the ECM, and podocytopenia – a mechanism not shared with endothelium and is distinct from drug-induced injury. Intriguingly, repopulation of hyperglycemia-injured podocytes on decellularized ECM scaffolds isolated from healthy podocytes attenuated the loss of synaptopodin (a mechanosensitive protein associated with podocyte health). These results demonstrate that human iPS cell-derived podocytes can facilitate <em>in vitro</em> studies to uncover the mechanisms of chronic hyperglycemia and ECM remodeling and guide disease target identification.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100164"},"PeriodicalIF":0.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone quality relies on hyaluronan synthesis – Insights from mice with complete knockout of hyaluronan synthase expression","authors":"A. Saalbach ,&nbsp;M. Stein ,&nbsp;S. Lee ,&nbsp;U. Krügel ,&nbsp;M. Haffner-Luntzer ,&nbsp;K. Krohn ,&nbsp;S. Franz ,&nbsp;J.C. Simon ,&nbsp;J. Tuckermann ,&nbsp;U. Anderegg","doi":"10.1016/j.mbplus.2024.100163","DOIUrl":"10.1016/j.mbplus.2024.100163","url":null,"abstract":"<div><div>Bone consists of a complex mineralised matrix that is maintained by a controlled equilibrium of synthesis and resorption by different cell types. Hyaluronan (HA) is an important glycosaminoglycan in many tissues including bone.</div><div>Previously, the importance of HA synthesis for bone development during embryogenesis has been shown. We therefore investigated whether HA synthesis is involved in adult bone turnover and whether abrogation of HA synthesis in adult mice would alter bone quality.</div><div>To achieve complete abrogation of HA synthesis in adult mice, we generated a novel Has-total knockout (Has-tKO) mouse model in which a constitutive knockout of Has1 and Has3 was combined with an inducible, Ubc-Cre-driven Has2 knockout.</div><div>By comparing bone tissue from wild-type, Has1,3 double knockout and Has-tKO mice, we demonstrate that Has2-derived HA mainly contributes to the HA content in bone. Furthermore, Has-tKO mice show a significant decrease of bone integrity in trabecular and cortical bone, as shown by µ-CT analysis. These effects are detectable as early as five weeks after induced Has2 deletion, irrespective of sex and progress with age.</div><div>Mesenchymal stem cells (MSC) during osteogenic differentiation <em>in vitro</em> showed that Has2 expression is increased while Has3 expression is decreased during differentiation. Furthermore, the complete abrogation of HA synthesis results in significantly reduced osteogenic differentiation as indicated by reduced marker gene expression (Runx-2, Tnalp, Osterix) as well as alizarin red staining. RNAseq analysis revealed that MSC from Has-tKO are characterised by decreased expression of genes annotated for bone and organ development, whereas expression of genes associated with chemokine related interactions and cytokine signalling is increased.</div><div>Taken together, we present a novel mouse model with complete deletion of HA synthases in adult mice which has the potential to study HA function in different organs and during age-related HA reduction. With respect to bone, HA synthesis is important for maintaining bone integrity, presumably based on the strong effect of HA on osteogenic differentiation.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of collagen and extracellular matrix deposition from cell culture using in vitro ExtraCellular matrix mass spectrometry imaging (ivECM-MSI)","authors":"Stephen C. Zambrzycki ,&nbsp;Samaneh Saberi ,&nbsp;Rachel Biggs ,&nbsp;Najmeh Eskandari ,&nbsp;Davide Delisi ,&nbsp;Harrison Taylor ,&nbsp;Anand S. Mehta ,&nbsp;Richard R. Drake ,&nbsp;Saverio Gentile ,&nbsp;Amy D. Bradshaw ,&nbsp;Michael Ostrowski ,&nbsp;Peggi M. Angel","doi":"10.1016/j.mbplus.2024.100161","DOIUrl":"10.1016/j.mbplus.2024.100161","url":null,"abstract":"<div><div>While numerous approaches have been reported towards understanding single cell regulation, there is limited understanding of single cell production of extracellular matrix phenotypes. Collagens are major proteins of the extracellular microenvironment extensively used in basic cell culture, tissue engineering, and biomedical applications. However, identifying compositional regulation of collagen remains challenging. Here, we report the development of In vitro ExtraCellular Matrix Mass Spectrometry Imaging (ivECM-MSI) as a tool to rapidly and simultaneously define collagen subtypes from coatings and basic cell culture applications. The tool uses the mass spectrometry imaging platform with reference libraries to produce visual and numerical data types. The method is highly integrated with basic in vitro strategies as it may be used with conventional cell chambers on minimal numbers of cells and with minimal changes to biological experiments. Applications tested include semi-quantitation of collagen composition in culture coatings, time course collagen deposition, deposition altered by gene knockout, and changes induced by drug treatment. This approach provides new access to proteomic information on how cell types respond to and change the extracellular microenvironment and provides a holistic understanding of both the cell and extracellular response.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-driven changes in breast tissue exhibit a pro-angiogenic extracellular matrix signature","authors":"Ellen E. Bamberg ,&nbsp;Mark Maslanka ,&nbsp;Kiran Vinod-Paul ,&nbsp;Sharon Sams ,&nbsp;Erica Pollack ,&nbsp;Matthew Conklin ,&nbsp;Peter Kabos ,&nbsp;Kirk C. Hansen","doi":"10.1016/j.mbplus.2024.100162","DOIUrl":"10.1016/j.mbplus.2024.100162","url":null,"abstract":"<div><div>Obesity has reached epidemic proportions in the United States, emerging as a risk factor for the onset of breast cancer and a harbinger of unfavorable outcomes <span><span>[1]</span></span>, <span><span>[2]</span></span>, <span><span>[3]</span></span>. Despite limited understanding of the precise mechanisms, both obesity and breast cancer are associated with extracellular matrix (ECM) rewiring <span><span>[4]</span></span>, <span><span>[5]</span></span>, <span><span>[6]</span></span>. Utilizing total breast tissue proteomics, we analyzed normal-weight (18.5 to &lt; 25 kg/m²), overweight (25 to &lt; 30 kg/m²), and obese (≥30 kg/m²) individuals to identify potential ECM modifying proteins for cancer development and acceleration. Obese individuals exhibited substantial ECM alterations, marked by increased basement membrane deposition, angiogenic signatures, and ECM-modifying proteins. Notably, the collagen IV crosslinking enzyme peroxidasin (PXDN) emerged as a potential mediator of the ECM changes in individuals with an elevated body mass index (BMI), strongly correlating with angiogenic and basement membrane signatures. Furthermore, glycan-binding proteins galectin-1 (LGALS1) and galectin-3 (LGALS3), which play crucial roles in matrix interactions and angiogenesis, also strongly correlate with ECM modifications. In breast cancer, elevated PXDN, LGALS1, and LGALS3 correlate with reduced relapse-free and distant-metastatic-free survival. These proteins were significantly associated with mesenchymal stromal cell markers, indicating adipocytes and fibroblasts may be the primary contributors of the obesity-related ECM changes. Our findings unveil a pro-angiogenic ECM signature in obese breast tissue, offering potential targets to inhibit breast cancer development and progression.</div></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of matrix in cardiomyogenesis: Defined substrates for maturation and chamber specificity","authors":"Jake Ireland ,&nbsp;Kristopher A. Kilian","doi":"10.1016/j.mbplus.2024.100160","DOIUrl":"10.1016/j.mbplus.2024.100160","url":null,"abstract":"<div><p>Human embryonic stem cell-derived cardiomyocytes (hESC-CM) are a promising source of cardiac cells for disease modelling and regenerative medicine. However, current protocols invariably lead to mixed population of cardiac cell types and often generate cells that resemble embryonic phenotypes. Here we developed a combinatorial approach to assess the importance of extracellular matrix proteins (ECMP) in directing the differentiation of cardiomyocytes from human embryonic stem cells (hESC). We did this by focusing on combinations of ECMP commonly found in the developing heart with a broad goal of identifying combinations that promote maturation and influence chamber specific differentiation. We formulated 63 unique ECMP combinations fabricated from collagen 1, collagen 3, collagen 4, fibronectin, laminin, and vitronectin, presented alone and in combinations, leading to the identification of specific ECMP combinations that promote hESC proliferation, pluripotency, and germ layer specification. When hESC were subjected to a differentiation protocol on the ECMP combinations, it revealed precise protein combinations that enhance differentiation as determined by the expression of cardiac progenitor markers kinase insert domain receptor (KDR) and mesoderm posterior transcription factor 1 (MESP1). High expression of cardiac troponin (cTnT) and the relative expression of myosin light chain isoforms (MLC2a and MLC2v) led to the identification of three surfaces that promote a mature cardiomyocyte phenotype. Action potential morphology was used to assess chamber specificity, which led to the identification of matrices that promote chamber-specific cardiomyocytes. This study provides a matrix-based approach to improve control over cardiomyocyte phenotypes during differentiation, with the scope for translation to cardiac laboratory models and for the generation of functional chamber specific cardiomyocytes for regenerative therapies.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"24 ","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000206/pdfft?md5=d5cecbae3ee49f649629c0a566f297f8&pid=1-s2.0-S2590028524000206-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic profiling of the extracellular matrix in the human adrenal cortex","authors":"Jean Lucas Kremer ,&nbsp;Henrique Sanchez Ortega ,&nbsp;Talita Souza-Siqueira ,&nbsp;Claudia Blanes Angeli ,&nbsp;Leo Kei Iwai ,&nbsp;Giuseppe Palmisano ,&nbsp;Claudimara Ferini Pacicco Lotfi","doi":"10.1016/j.mbplus.2024.100158","DOIUrl":"10.1016/j.mbplus.2024.100158","url":null,"abstract":"<div><p>The extracellular matrix (ECM) comprises macromolecules that shape a complex three-dimensional network. Filling the intercellular space and playing a crucial role in the structure and function of tissues, ECM regulates essential cellular processes such as adhesion, differentiation, and cell signaling. In the human adrenal gland, composed of cortex and medulla surrounded by a capsule, the ECM has not yet been directly described, although its impact on the processes of proliferation and steroidogenesis of the adrenal cortex is recognized. This study analyzes the ECM of the adult human adrenal cortex, which was separated into outer fraction (OF) and inner fraction (IF), by comparing their proteomic profiles. The study discusses the composition, spatial distribution, and relevance of differentially expressed ECM signatures of the adrenal cortex matrisome on adrenal structure and function. The findings were validated through database analysis (cross-validation), histochemical, and immunohistochemical approaches. A total of 121 ECM proteins were identified and categorized into glycoproteins, collagens, ECM regulators, proteoglycans, ECM-affiliated proteins, and secreted factors. Thirty-one ECM proteins were identified only in OF, nine only in IF, and 81 were identified in common with both fractions. Additionally, 106 ECM proteins were reported in the Human matrisome DB 2.0, and the proteins differentially expressed in OF and IF, were identified. This study provides significant insights into the composition and regulation of the ECM in the human adrenal cortex, shedding light on the adrenal microenvironment and its role in the functioning, maintenance, and renewal of the adrenal gland.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000188/pdfft?md5=cfc1b36c2953d4b9d1fcbeb6a6166497&pid=1-s2.0-S2590028524000188-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cartilage-derived cells display heterogeneous pericellular matrix synthesis in agarose microgels","authors":"Marloes van Mourik ,&nbsp;Bart M. Tiemeijer ,&nbsp;Maarten van Zon ,&nbsp;Florencia Abinzano ,&nbsp;Jurjen Tel ,&nbsp;Jasper Foolen ,&nbsp;Keita Ito","doi":"10.1016/j.mbplus.2024.100157","DOIUrl":"10.1016/j.mbplus.2024.100157","url":null,"abstract":"<div><p>The pericellular matrix (PCM) surrounding chondrocytes is essential for articular cartilage tissue engineering. As the current isolation methods to obtain chondrocytes with their PCM (chondrons) result in a heterogeneous mixture of chondrocytes and chondrons, regenerating the PCM using a tissue engineering approach could prove beneficial. In this study, we aimed to discern the behavior of articular chondrocytes (ACs) in regenerating the PCM in such an approach and whether this would also be true for articular cartilage-derived progenitor cells (ACPCs), as an alternative cell source. Bovine ACs and ACPCs were encapsulated in agarose microgels using droplet-based microfluidics. ACs were stimulated with TGF-β1 and dexamethasone and ACPCs were sequentially stimulated with BMP-9 followed by TGF-β1 and dexamethasone. After 0, 3, 5, and 10 days of culture, PCM components, type-VI collagen and perlecan, and ECM component, type-II collagen, were assessed using flow cytometry and fluorescence microscopy. Both ACs and ACPCs synthesized the PCM before the ECM. It was seen for the first time that synthesis of type-VI collagen always preceded perlecan. While the PCM synthesized by ACs resembled native chondrons after only 5 days of culture, ACPCs often made less well-structured PCMs. Both cell types showed variations between individual cells and donors. On one hand, this was more prominent in ACPCs, but also a subset of ACPCs showed superior PCM and ECM regeneration, suggesting that isolating these cells may potentially improve cartilage repair strategies.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000176/pdfft?md5=a6314ad1e2b54f25ca6e30f6af88488b&pid=1-s2.0-S2590028524000176-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrisome proteomics reveals novel mediators of muscle remodeling with aerobic exercise training","authors":"Pattarawan Pattamaprapanont ,&nbsp;Eileen M. Cooney ,&nbsp;Tara L. MacDonald ,&nbsp;Joao A. Paulo ,&nbsp;Hui Pan ,&nbsp;Jonathan M. Dreyfuss ,&nbsp;Sarah J. Lessard","doi":"10.1016/j.mbplus.2024.100159","DOIUrl":"10.1016/j.mbplus.2024.100159","url":null,"abstract":"<div><p>Skeletal muscle has a unique ability to remodel in response to stimuli such as contraction and aerobic exercise training. Phenotypic changes in muscle that occur with training such as a switch to a more oxidative fiber type, and increased capillary density contribute to the well-known health benefits of aerobic exercise. The muscle matrisome likely plays an important role in muscle remodeling with exercise. However, due to technical limitations in studying muscle ECM proteins, which are highly insoluble, little is known about the muscle matrisome and how it contributes to muscle remodeling. Here, we utilized two-fraction methodology to extract muscle proteins, combined with multiplexed tandem mass tag proteomic technology to identify 161 unique ECM proteins in mouse skeletal muscle. In addition, we demonstrate that aerobic exercise training induces remodeling of a significant proportion of the muscle matrisome. We performed follow-up experiments to validate exercise-regulated ECM targets in a separate cohort of mice using Western blotting and immunofluorescence imaging. Our data demonstrate that changes in several key ECM targets are strongly associated with muscle remodeling processes such as increased capillary density in mice. We also identify LOXL1 as a novel muscle ECM target associated with aerobic capacity in humans. In addition, publically available data and databases were used for in silico modeling to determine the likely cellular sources of exercise-induced ECM remodeling targets and identify ECM interaction networks. This work greatly enhances our understanding of ECM content and function in skeletal muscle and demonstrates an important role for ECM remodeling in the adaptive response to exercise. The raw MS data have been deposited to the ProteomeXchange with identifier PXD053003.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100159"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259002852400019X/pdfft?md5=f9ac69cc862df261d53366122e2ba4fa&pid=1-s2.0-S259002852400019X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of cancer cell line and tissue RNA sequencing data reveals an essential and dark matrisome","authors":"Joshua A. Rich ,&nbsp;Yu Fan ,&nbsp;Qingrong Chen ,&nbsp;Daoud Meerzaman ,&nbsp;William G. Stetler-Stevenson ,&nbsp;David Peeney","doi":"10.1016/j.mbplus.2024.100156","DOIUrl":"https://doi.org/10.1016/j.mbplus.2024.100156","url":null,"abstract":"<div><p>Extracellular matrix remodeling is a hallmark of tissue development, homeostasis, and disease. The processes that mediate remodeling, and the consequences of such, are the topic of extensive focus in biomedical research. Cell culture methods represent a crucial tool utilized by those interested in matrisome function, the easiest of which are implemented with immortalized/cancer cell lines. These cell lines often form the foundations of a research proposal, or serve as vehicles of validation for other model systems. For these reasons, it is important to understand the complement of matrisome genes that are expressed when identifying appropriate cell culture models for hypothesis testing. To this end, we harvested bulk RNA sequencing data from the Cancer Cell Line Encyclopedia (CCLE) to assess matrisome gene expression in 1019 human cell lines. Our examination reveals that a large proportion of the matrisome is poorly represented in human cancer cell lines, with approximately 10% not expressed above threshold in any of the cell lines assayed. Conversely, we identify clusters of essential/common matrisome genes that are abundantly expressed in cell lines. To validate these observations against tissue data, we compared our findings with bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) portal and The Cancer Genome Atlas (TCGA) program. This comparison demonstrates general agreement between the “essential/common” and “dark/uncommon” matrisome across the three datasets, albeit with discordance observed in 59 matrisome genes between cell lines and tissues. Notably, all of the discordant genes are essential/common in tissues yet minimally expressed in cell lines, underscoring critical considerations for matrix biology researchers employing immortalized cell lines for their investigations.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000164/pdfft?md5=243092e6a458f09effb7c337f5b72353&pid=1-s2.0-S2590028524000164-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141483835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue material properties, whole-bone morphology and mechanical behavior in the Fbn1C1041G/+ mouse model of Marfan syndrome","authors":"Elizabeth A. Zimmermann ,&nbsp;Taylor DeVet ,&nbsp;Myriam Cilla ,&nbsp;Laia Albiol ,&nbsp;Kyle Kavaseri ,&nbsp;Christine Andrea ,&nbsp;Catherine Julien ,&nbsp;Kerstin Tiedemann ,&nbsp;Arash Panahifar ,&nbsp;Sima A. Alidokht ,&nbsp;Richard Chromik ,&nbsp;Svetlana V. Komarova ,&nbsp;Dieter P. Reinhardt ,&nbsp;Paul Zaslansky ,&nbsp;Bettina M. Willie","doi":"10.1016/j.mbplus.2024.100155","DOIUrl":"10.1016/j.mbplus.2024.100155","url":null,"abstract":"<div><p>Marfan syndrome (MFS) is a connective tissue disorder caused by pathogenic mutations in FBN1. In bone, the protein fibrillin-1 is found in the extracellular matrix where it provides structural support of elastic fiber formation, stability for basement membrane, and regulates the bioavailability of growth factors. Individuals with MFS exhibit a range of skeletal complications including low bone mineral density and long bone overgrowth. However, it remains unknown if the bone phenotype is caused by alteration of fibrillin-1′s structural function or distortion of its interactions with bone cells. To assess the structural effects of the fibrillin-1 mutation, we characterized bone curvature, microarchitecture, composition, porosity, and mechanical behavior in the <em>Fbn1</em>^C1041G/+ mouse model of MFS. Tibiae of 10, 26, and 52-week-old female <em>Fbn1</em>^C1041G/+ and littermate control (LC) mice were analyzed. Mechanical behavior was assessed via in vivo strain gauging, finite element analysis, <em>ex vivo</em> three-point bending, and nanoindentation. Tibial bone morphology and curvature were assessed with micro computed tomography (μCT). Bone composition was measured with Fourier transform infrared (FTIR) imaging. Vascular and osteocyte lacunar porosity were assessed by synchrotron computed tomography. <em>Fbn1</em>^C1041G/+ mice exhibited long bone overgrowth and osteopenia consistent with the MFS phenotype. Trabecular thickness was lower in <em>Fbn1</em>^C1041G/+ mice but cortical bone microarchitecture was similar in <em>Fbn1</em>^C1041G/+ and LC mice. Whole bone curvature was straighter below the tibio-fibular junction in the medial–lateral direction and more curved above in LC compared to <em>Fbn1</em>^C1041G/+ mice. The bone matrix crystallinity was 4 % lower in <em>Fbn1</em>^C1041G/+ mice compared to LC, implying that mineral platelets in LCs have greater crystal size and perfection than <em>Fbn1</em>^C1041G/+ mice. Structural and mechanical properties were similar between genotypes. Cortical diaphyseal lacunar porosity was lower in <em>Fbn1</em>^C1041G/+ mice compared to LC; this was a result of the average volume of an individual osteocyte lacunae being smaller. These data provide valuable insights into the bone phenotype and its contribution to fracture risk in this commonly used mouse model of MFS.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"23 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590028524000152/pdfft?md5=aa5b85d8cec6470f016ad8dea315109f&pid=1-s2.0-S2590028524000152-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141406658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}