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For many years there has been a keen interest in developing regenerative treatment for temporomandibular joint-osteoarthritis (TMJ-OA). Currently, there is no consensus treatment due to the limited self-healing ability of articular cartilage and lack of understanding of the complex mechanisms regulating cartilage development in the TMJ. Endochondral ossification, the process of subchondral bone formation through chondrocyte differentiation, is critical for TMJ growth and development, and is tightly regulated by the composition of the extracellular matrix (ECM). Type VI collagen is a highly expressed ECM component in the TMJ cartilage, yet its specific functions are largely unknown. In this study, we investigated α2(VI)-deficient (Col6a2-knockout [KO]) mice, which are unable to secret or incorporate type VI collagen into their ECM. Compared with wild-type (WT) mice, the TMJ condyles of Col6a2-KO mice exhibit decreased bone volume/tissue volume (BV/TV) and a larger bone marrow space, suggesting the α2(VI)-deficient condyles have a failure in endochondral ossification. Differentiating chondrocytes are the main source of bone cells during endochondral ossification. Our study shows there is an increased number of chondrocytes in the proliferative zone and decreased Col10-expressing chondrocytes in Col6a2-KO cartilage, all pointing to abnormal chondrocyte differentiation and maturation. In addition, RNA sequencing (RNAseq) analysis identified distinct gene expression profiles related to cell cycle and ECM organization that were altered in the mutant condyles. These data also suggest that bone morphogenetic protein 2 (BMP2) activity was deregulated during chondrocyte differentiation. Immunohistochemical analysis indicated an upregulation of Col2 and Acan expression in Col6a2-KO cartilage. Moreover, the expression of pSmad1/5/8 and Runx2 was decreased in the Col6a2-KO cartilage compared with WT controls. Taken together, our data indicate that type VI collagen expressed in the TMJ cartilage is important for endochondral ossification, possibly by modulating the ECM and altering/disrupting signaling pathways important for TMJ chondrocyte differentiation. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Pubmed ID: 35509631
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A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsSoftware environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsSoftware package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsQuality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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