Dataset Information

Role of Fibulin 3 in Aging-Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage.

ABSTRACT: The EFEMP1 gene encoding fibulin 3 is specifically expressed in the superficial zone (SZ) of articular cartilage. The aims of this study were to examine the expression patterns of fibulin 3 in the knee joints during aging and during osteoarthritis (OA) and to determine the role of fibulin 3 in the pathogenesis of OA.Immunohistochemical analysis was performed on normal and OA knee cartilage samples from humans and mice. Experimental OA was induced in wild-type and fibulin 3-/- mice, and the severity of OA was evaluated by histologic scoring. To examine fibulin 3 function, human chondrocyte monolayer cultures were transfected with small interfering RNA (siRNA), followed by quantitative polymerase chain reaction and Western blot analyses. Human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transduced with an EFEMP1 lentivirus and analyzed for markers of chondrogenesis.Fibulin 3 was specifically expressed in the SZ of normal knee joint cartilage from humans and mice, and the expression levels declined with aging. Both aging-related OA and experimental OA were significantly more severe in fibulin 3-/- mice compared with wild-type mice. Fibulin 3 expression was high in undifferentiated human BM-MSCs and decreased during chondrogenesis. Suppression of fibulin 3 by siRNA significantly increased the expression of SOX9, type II collagen, and aggrecan in human articular chondrocytes, while overexpression of fibulin 3 inhibited chondrogenesis in BM-MSCs.Fibulin 3 is specifically expressed in the SZ of articular cartilage and its expression is reduced in aging and OA. Fibulin 3 regulates differentiation of adult progenitor cells, and its aging-related decline is an early event in the pathogenesis of OA. Preventing aging-associated loss of fibulin 3 or restoring it to normal levels in SZ chondrocytes has the potential to delay or prevent the onset of OA.

SUBMITTER: Hasegawa A

PROVIDER: S-EPMC5328782 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Role of Fibulin 3 in Aging-Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage.

Hasegawa Akihiko A Yonezawa Tomo T Taniguchi Noboru N Otabe Koji K Akasaki Yukio Y Matsukawa Tetsuya T Saito Masahiko M Neo Masashi M Marmorstein Lihua Y LY Lotz Martin K MK

Arthritis & rheumatology (Hoboken, N.J.) 20170301 3

<h4>Objective</h4>The EFEMP1 gene encoding fibulin 3 is specifically expressed in the superficial zone (SZ) of articular cartilage. The aims of this study were to examine the expression patterns of fibulin 3 in the knee joints during aging and during osteoarthritis (OA) and to determine the role of fibulin 3 in the pathogenesis of OA.<h4>Methods</h4>Immunohistochemical analysis was performed on normal and OA knee cartilage samples from humans and mice. Experimental OA was induced in wild-type an ...[more]

PMID: 27780308

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Project description:Objectives:The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods:The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results:In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1?-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion:This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients.Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:288-301. DOI: 10.1302/2046-3758.86.BJR-2018-0297.R1.

Project description:ObjectivesThe aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA).MethodsThe expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo.ResultsIn total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues.ConclusionThis study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients.Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290-303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.R1.

Dataset Information

Role of Fibulin 3 in Aging-Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage.

Publications

Role of Fibulin 3 in Aging-Related Joint Changes and Osteoarthritis Pathogenesis in Human and Mouse Knee Cartilage.

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