Matrix Biology最新文献

{"title":"Myeloid deficiency of heparan sulfate 6-O-endosulfatases impairs bone marrow hematopoiesis","authors":"Anna K. Whitehead ,&nbsp;Zhangjie Wang ,&nbsp;Rebecca-Joe Boustany ,&nbsp;Romain R. Vivès ,&nbsp;Eric Lazartigues ,&nbsp;Jian Liu ,&nbsp;Robert W. Siggins ,&nbsp;Xinping Yue","doi":"10.1016/j.matbio.2024.10.002","DOIUrl":"10.1016/j.matbio.2024.10.002","url":null,"abstract":"<div><div>The heparan sulfate (HS) 6-<em>O</em>-endosulfatases or the Sulfs (Sulf1 and Sulf2) are the only known enzymes that can modify HS sulfation status extracellularly and have been shown to regulate diverse biological processes. The role of the Sulfs in bone marrow (BM) hematopoiesis is not known. In this study, we generated a novel mouse line with myeloid-specific deletion of the Sulfs by crossing Sulf1/2 double floxed mice with the <em>LysM-cre</em> line. The <em>LysM-Sulf</em> knockout (KO) male mice exhibited age-dependent expansion of hematopoietic stem cells and the granulocyte-monocyte lineages in the BM, whereas common lymphoid progenitors and B lymphocyte populations were significantly reduced. Although megakaryocytic and erythroid progenitors were not reduced in the BM, the <em>LysM-Sulf</em> KO males suffered age-dependent reduction of red blood cells (RBCs) and platelets in the peripheral blood, suggesting that the production of RBCs and platelets was arrested at later stages. In addition, <em>LysM-Sulf</em> KO males displayed progressive splenomegaly with extramedullary hematopoiesis. Compared to males, <em>LysM-Sulf</em> KO females exhibited a much-reduced phenotype, and ovariectomy had little effect. Mechanistically, reduced TGF-β/Smad2 but enhanced p53/p21 signaling were observed in male but not female <em>LysM-Sulf</em> KO mice. Finally, HS disaccharide analysis via LC-MS/MS revealed increased HS 6-<em>O</em>-sulfation in the BM from both male and female <em>LysM-Sulf</em> KO mice, however, the distribution of 6-<em>O</em>-sulfated motifs were different between the sexes with compensatory increase in Sulf1 expression observed only in <em>LysM-Sulf</em> KO females. In conclusion, our study reveals that myeloid deficiency of the Sulfs leads to multilineage abnormalities in BM hematopoiesis in an age- and sex-dependent manner.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 107-118"},"PeriodicalIF":4.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix vesicles from osteoblasts promote atherosclerotic calcification","authors":"Xiaoli Wang ,&nbsp;Jie Ren ,&nbsp;Fei Fang ,&nbsp;Erxiang Wang ,&nbsp;Jianwei Li ,&nbsp;Weihong He ,&nbsp;Zhen Zhang ,&nbsp;Yang Shen ,&nbsp;Xiaoheng Liu","doi":"10.1016/j.matbio.2024.09.003","DOIUrl":"10.1016/j.matbio.2024.09.003","url":null,"abstract":"<div><div>Atherosclerotic calcification often coincides with osteoporosis, suggesting a potential interplay between bone and vascular mineralization. Osteoblast-derived matrix vesicles (Ost-MVs), pivotal in bone mineralization, have emerged as potential contributors to ectopic vascular calcification. However, the precise role of Ost-MVs in vascular calcification and the underlying mechanisms remain elusive. In this study, we observed a concomitant increase in atherosclerotic calcification and bone loss, accompanied by elevated release of Ost-MVs into circulation. We demonstrate that circulating Ost-MVs target plaque lesions in the setting of atherosclerosis. Mechanistically, vascular injury facilitates transendothelial transport of Ost-MVs, collagen І remodeling promotes Ost-MVs aggregation, and vascular smooth muscle cell (VSMC) phenotypic switching enhances MV uptake. These pathological changes during atherosclerosis collectively contribute to Ost-MVs recruitment into the vasculature. Furthermore, Ost-MVs and VSMC-derived matrix vesicles (VSMC-MVs) exacerbate calcification via the Ras-Raf-ERK pathway. Our findings unveil a novel Ost-MVs-mediated mechanism participating in vascular calcification and enriching our understanding of bone-vascular crosstalk.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 79-92"},"PeriodicalIF":4.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of osteosarcoma metastasis in vivo by targeted downregulation of MMP1 and MMP9","authors":"Ofri Doppelt-Flikshtain ,&nbsp;Thabet Asbi ,&nbsp;Amin Younis ,&nbsp;Ofir Ginesin ,&nbsp;Ziv Cohen ,&nbsp;Tal Tamari ,&nbsp;Tal Berg ,&nbsp;Chen Yanovich ,&nbsp;Dvir Aran ,&nbsp;Yaniv Zohar ,&nbsp;Yehuda G. Assaraf ,&nbsp;Hadar Zigdon-Giladi","doi":"10.1016/j.matbio.2024.09.002","DOIUrl":"10.1016/j.matbio.2024.09.002","url":null,"abstract":"<div><p>Osteosarcoma (OS) mortality stems from lung metastases. Matrix metalloproteinases (MMPs) facilitate metastatic dissemination by degrading extracellular matrix components. Herein we studied the impact of targeted MMP downregulation on OS metastasis. Differential gene expression analysis of human OS cell lines revealed high MMP9 expression in the majority of OS cell lines. Furthermore, 143B, a metastatic OS cell line, exhibited increased MMP1 and MMP9 mRNA levels. Gene set enrichment analysis on metastatic and non-metastatic OS patient specimens indicated epithelial-mesenchymal transition as the most enriched gene set, with MMP9 displaying strong association to genes in this network. Using the same dataset, Kaplan-Meier analysis revealed a correlation between MMP1 expression and dismal patient survival. Hence, we undertook targeted suppression of MMP1 and MMP9 gene expression in OS cell lines. The ability of OS cells to migrate and form colonies was markedly reduced upon MMP1 and MMP9 downregulation, whereas their cell proliferation capacity remained intact. MMP9 downregulation decreased tumor growth and lung metastases area in an orthotopic mouse OS model. Consistently, human OS lung metastasis specimens displayed marked MMP9 protein expression. Our findings highlight the role of MMP1 and MMP9 in OS metastasis, warranting further exploration of simultaneous inhibition of MMPs for future OS therapeutics.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 48-58"},"PeriodicalIF":4.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCPE-2 (procollagen C-proteinase enhancer-2): The non-identical twin of PCPE-1","authors":"Manon Napoli,&nbsp;Julien Bauer,&nbsp;Christelle Bonod,&nbsp;Sandrine Vadon-Le Goff,&nbsp;Catherine Moali","doi":"10.1016/j.matbio.2024.09.001","DOIUrl":"10.1016/j.matbio.2024.09.001","url":null,"abstract":"<div><div>PCPE-2 was discovered at the beginning of this century, and was soon identified as a close homolog of PCPE-1 (procollagen C-proteinase enhancer 1). After the demonstration that it could also stimulate the proteolytic maturation of fibrillar procollagens by BMP-1/tolloid-like proteinases (BTPs), PCPE-2 did not attract much attention as it was thought to fulfill the same functions as PCPE-1 which was already well-described. However, the tissue distribution of PCPE-2 shows both common points and significant differences with PCPE-1, suggesting that their activities are not fully overlapping. Also, the recently established connections between PCPE-2 (gene name <em>PCOLCE2</em>) and several important diseases such as atherosclerosis, inflammatory diseases and cancer have highlighted the need for a thorough reappraisal of the <em>in vivo</em> roles of this regulatory protein. In this context, the recent finding that, while retaining the ability to bind fibrillar procollagens and to activate their C-terminal maturation, PCPE-2 can also bind BTPs and inhibit their activity has substantially extended its potential functions. In this review, we describe the current knowledge about PCPE-2 with a focus on collagen fibrillogenesis, lipid metabolism and inflammation, and discuss how we could further advance our understanding of PCPE-2-dependent biological processes.</div></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 59-78"},"PeriodicalIF":4.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24001136/pdfft?md5=9dc9c6cca3ca66f81f90fa581c90b323&pid=1-s2.0-S0945053X24001136-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The integral role of fibronectin in skeletal morphogenesis and pathogenesis","authors":"Neha E.H. Dinesh ,&nbsp;Philippe M. Campeau ,&nbsp;Dieter P. Reinhardt","doi":"10.1016/j.matbio.2024.08.010","DOIUrl":"10.1016/j.matbio.2024.08.010","url":null,"abstract":"<div><p>Fibronectin (FN) serves as a critical organizer of extracellular matrix networks in two principal isoforms, the plasma FN and the cellular FN. While FN's pivotal role in various organ systems, including the blood vasculature, is well-established, its contribution to the development of the skeletal system is much less explored. Furthermore, the pathomechanisms of spondyloepiphyseal dysplasia caused by FN mutations remain elusive. In this minireview, we discuss findings from our recent two studies using i) an iPSC-based cell culture model to explore how FN mutations in spondyloepiphyseal dysplasia impact mesenchymal cell differentiation into chondrocytes and ii) conditional FN knockout mouse models to determine the physiological roles of FN isoforms during postnatal skeletal development. The data revealed that FN mutations cause severe intracellular and matrix defects in mesenchymal cells and impair their ability to differentiate into chondrocytes. The findings further demonstrate the important roles of both FN isoforms in orchestrating regulated chondrogenesis during skeletal development. We critically discuss the findings in the context of the existing literature.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 23-29"},"PeriodicalIF":4.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24001124/pdfft?md5=fc897326a5dda1250b7a01f792bd5f81&pid=1-s2.0-S0945053X24001124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronan and proteoglycan link protein 1 – A novel signaling molecule for rejuvenating aged skin","authors":"Zhicheng Fu ,&nbsp;Goowon Yang ,&nbsp;So Yoon Yun ,&nbsp;Ji Min Jang ,&nbsp;Hae Chan Ha ,&nbsp;In Chul Shin ,&nbsp;Moon Jung Back ,&nbsp;Yongwei Piao ,&nbsp;Dae Kyong Kim","doi":"10.1016/j.matbio.2024.08.009","DOIUrl":"10.1016/j.matbio.2024.08.009","url":null,"abstract":"<div><p>The skin seems to rejuvenate upon exposure to factors within the circulation of young organisms. Intrinsic factors that modulate skin aging are poorly understood. We used heterochronic parabiosis and aptamer-based proteomics to identify serum-derived rejuvenating factors. We discovered a novel extracellular function of hyaluronan and proteoglycan link protein 1 (HAPLN1). Its serum levels decreased with age, disturbing the integrity of the skin extracellular matrix, which is predominantly composed of collagen I and hyaluronan; levels of various markers, which decrease in aged skin, were significantly restored <em>in vivo</em> and <em>in vitro</em> by the administration of recombinant human HAPLN1 (rhHAPLN1). rhHAPLN1 protected transforming growth factor beta receptor 2 on the cell surface from endocytic degradation via mechanisms such as regulation of viscoelasticity, CD44 clustering. Moreover, rhHAPLN1 regulated the levels of nuclear factor erythroid 2–related factor 2, phosphorylated nuclear factor kappa B, and some cyclin-dependent kinase inhibitors such as p16 and p21. Therefore, rhHAPLN1 may act as a novel biomechanical signaling protein to rejuvenate aged skin.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 30-47"},"PeriodicalIF":4.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24001112/pdfft?md5=8ab084cfcac6cfeb61b9acc8b5b4bb38&pid=1-s2.0-S0945053X24001112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myocardial fibrosis from the perspective of the extracellular matrix: Mechanisms to clinical impact","authors":"Ida G. Lunde ,&nbsp;Karoline B. Rypdal ,&nbsp;Sophie Van Linthout ,&nbsp;Javier Diez ,&nbsp;Arantxa González","doi":"10.1016/j.matbio.2024.08.008","DOIUrl":"10.1016/j.matbio.2024.08.008","url":null,"abstract":"<div><p>Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and constitutes a central pathophysiological process that underlies tissue dysfunction, across organs, in multiple chronic diseases and during aging. Myocardial fibrosis is a key contributor to dysfunction and failure in numerous diseases of the heart and is a strong predictor of poor clinical outcome and mortality. The excess structural and matricellular ECM proteins deposited by cardiac fibroblasts, is found between cardiomyocytes (interstitial fibrosis), in focal areas where cardiomyocytes have died (replacement fibrosis), and around vessels (perivascular fibrosis). Although myocardial fibrosis has important clinical prognostic value, access to cardiac tissue biopsies for histological evaluation is limited. Despite challenges with sensitivity and specificity, cardiac magnetic resonance imaging (CMR) is the most applicable diagnostic tool in the clinic, and the scientific community is currently actively searching for blood biomarkers reflecting myocardial fibrosis, to complement the imaging techniques. The lack of mechanistic insights into specific pro- and anti-fibrotic molecular pathways has hampered the development of effective treatments to prevent or reverse myocardial fibrosis. Development and implementation of anti-fibrotic therapies is expected to improve patient outcomes and is an urgent medical need. Here, we discuss the importance of the ECM in the heart, the central role of fibrosis in heart disease, and mechanistic pathways likely to impact clinical practice with regards to diagnostics of myocardial fibrosis, risk stratification of patients, and anti-fibrotic therapy.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"134 ","pages":"Pages 1-22"},"PeriodicalIF":4.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemic environments directly compromise intestinal epithelial barrier function in an organoid model and hyaluronan (∼35 kDa) protects via a layilin dependent mechanism","authors":"Samreen Jatana ,&nbsp;Amina Abbadi ,&nbsp;Gail A. West ,&nbsp;András K. Ponti ,&nbsp;Manuel B. Braga-Neto ,&nbsp;Jordyn L. Smith ,&nbsp;Armando Marino-Melendez ,&nbsp;Belinda Willard ,&nbsp;Laura E. Nagy ,&nbsp;Carol de la Motte","doi":"10.1016/j.matbio.2024.08.007","DOIUrl":"10.1016/j.matbio.2024.08.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Metabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) and colorectal cancer. The pathogenic mechanisms of low-grade metabolic inflammation, including chronic hyperglycemic stress, in disrupting gut homeostasis are poorly understood. In this study, we sought to understand the impact of a hyperglycemic environment on intestinal barrier integrity and the protective effects of small molecular weight (35 kDa) hyaluronan on epithelial barrier function.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Intestinal organoids derived from mouse colon were grown in normal glucose media (5 mM) or high glucose media (25 mM) to study the impact of hyperglycemic stress on the intestinal barrier. Additionally, organoids were pretreated with 35 kDa hyaluronan (HA35) to investigate the effect of hyaluronan on epithelial barrier under high glucose stress. Immunoblotting as well as confocal imaging was used to understand changes in barrier proteins, quantitative as well as spatial distribution, respectively. Alterations in barrier function were measured using trans-epithelial electrical resistance and fluorescein isothiocyanate flux assays. Untargeted proteomics analysis was performed to elucidate mechanisms by which HA35 exerts a protective effect on the barrier. Intestinal organoids derived from receptor knockout mice specific to various HA receptors were utilized to understand the role of HA receptors in barrier protection under high glucose conditions.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;We found that high glucose stress decreased the protein expression as well as spatial distribution of two key barrier proteins, zona occludens-1 (ZO-1) and occludin. HA35 prevented the degradation or loss of ZO-1 and maintained the spatial distribution of both ZO-1 and occludin under hyperglycemic stress. Functionally, we also observed a protective effect of HA35 on the epithelial barrier under high glucose conditions. We found that HA receptor, layilin, was involved in preventing barrier protein loss (ZO-1) as well as maintaining spatial distribution of ZO-1 and occludin. Additionally, proteomics analysis showed that cell death and survival was the primary pathway upregulated in organoids treated with HA35 under high glucose stress. We found that XIAP associated factor 1 (Xaf1) was modulated by HA35 thereby regulating apoptotic cell death in the intestinal organoid system. Finally, we observed that spatial organization of both focal adhesion kinase (FAK) as well as F-actin was mediated by HA35 via layilin.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Our results highlight the impact of hyperglycemic stress on the intestinal barrier function. This is of clinical relevance, as impaired barrier function has been observed in individuals with metabolic syndrome. Additionally, we demonstrate barrier protective effects of HA35 through its receptor layilin and modulation of cellular apoptosis under high glucose st","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"133 ","pages":"Pages 116-133"},"PeriodicalIF":4.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24001094/pdfft?md5=1c766d0c9cca2bc04493949f2a75f84f&pid=1-s2.0-S0945053X24001094-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibronectin isoforms promote postnatal skeletal development","authors":"Neha E.H. Dinesh ,&nbsp;Nissan Baratang ,&nbsp;Justine Rosseau ,&nbsp;Ronit Mohapatra ,&nbsp;Ling Li ,&nbsp;Ramshaa Mahalingam ,&nbsp;Kerstin Tiedemann ,&nbsp;Philippe M. Campeau ,&nbsp;Dieter P. Reinhardt","doi":"10.1016/j.matbio.2024.08.002","DOIUrl":"10.1016/j.matbio.2024.08.002","url":null,"abstract":"<div><p>Fibronectin (FN) is a ubiquitous extracellular matrix glycoprotein essential for the development of various tissues. Mutations in FN cause a unique form of spondylometaphyseal dysplasia, emphasizing its importance in cartilage and bone development. However, the relevance and functional role of FN during skeletal development has remained elusive. To address these aspects, we have generated conditional knockout mouse models targeting the cellular FN isoform in cartilage (cFNKO), the plasma FN isoform in hepatocytes (pFNKO), and both isoforms together in a double knockout (FNdKO). We used these mice to determine the relevance of the two principal FN isoforms in skeletal development from postnatal day one to the adult stage at two months.</p><p>We identified a distinct topological FN deposition pattern in the mouse limb during different gestational and postnatal skeletal development phases, with prominent levels at the resting and hypertrophic chondrocyte zones and in the trabecular bone. Cartilage-specific cFN emerged as the predominant isoform in the growth plate, whereas circulating pFN remained excluded from the growth plate and confined to the primary and secondary ossification centers. Deleting either isoform independently (cFNKO or pFNKO) yielded only relatively subtle changes in the analyzed skeletal parameters. However, the double knockout of cFN in the growth plate and pFN in the circulation of the FNdKO mice significantly reduced postnatal body weight, body length, and bone length. Micro-CT analysis of the adult bone microarchitecture in FNdKO mice exposed substantial reductions in trabecular bone parameters and bone mineral density. The mice also showed elevated bone marrow adiposity. Analysis of chondrogenesis in FNdKO mice demonstrated changes in the resting, proliferating and hypertrophic growth plate zones, consistent alterations in chondrogenic markers such as collagen type II and X, decreased apoptosis of hypertrophic chondrocytes, and downregulation of bone formation markers. Transforming growth factor-β1 and downstream phospho-AKT levels were significantly lower in the FNdKO than in the control mice, revealing a crucial FN-mediated regulatory pathway in chondrogenesis and bone formation.</p><p>In conclusion, the data demonstrate that FN is essential for chondrogenesis and bone development. Even though cFN and pFN act in different regions of the bone, both FN isoforms are required for the regulation of chondrogenesis, cartilage maturation, trabecular bone formation, and overall skeletal growth.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"133 ","pages":"Pages 86-102"},"PeriodicalIF":4.5,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24001045/pdfft?md5=223df76f43eebcd53906b944c05aa90b&pid=1-s2.0-S0945053X24001045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collagen VIII in vascular diseases","authors":"Qian Li ,&nbsp;Yin Tintut ,&nbsp;Linda L. Demer ,&nbsp;Roberto I. Vazquez-Padron ,&nbsp;Michelle P. Bendeck ,&nbsp;Jeffrey J. Hsu","doi":"10.1016/j.matbio.2024.08.006","DOIUrl":"10.1016/j.matbio.2024.08.006","url":null,"abstract":"<div><p>Collagens have dual functions in the extracellular matrix (ECM), acting as both structural components and signaling molecules in matricellular communication. Although collagen molecules share a common triple helix motif, the supramolecular organization helps classify them into nearly 30 different types of collagens. Collagen type VIII is a non-fibrillar, short-chain, network-forming collagen that is expressed throughout the vasculature. Collagen VIII expression is aberrant in cardiovascular, lung, and renal disease, as well as in several different types of cancer. It plays active roles in angiogenesis, vessel injury repair, maintenance of arterial compliance, atherosclerotic plaque formation and stability modulation, fibrosis, and ECM remodeling. This review presents an overview of the characteristics of collagen VIII in vascular-related disorders, from clinical significance to laboratory studies, with a major focus on highlighting the signaling properties of collagen VIII in the vascular ECM. The expression patterns of collagen VIII in human diseases and experimental animal models highlight the protein's important yet underexplored functions. A deeper understanding of its mechanisms and downstream signaling pathways may pave the way for translational and tissue engineering applications of collagen VIII.</p></div>","PeriodicalId":49851,"journal":{"name":"Matrix Biology","volume":"133 ","pages":"Pages 64-76"},"PeriodicalIF":4.5,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0945053X24001082/pdfft?md5=a798c7eb53554e941e24cc81d0b60dd5&pid=1-s2.0-S0945053X24001082-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}