Dataset Information

Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process.

ABSTRACT: Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiple in vivo approaches to study the role of Bmpr1a in endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure when Bmpr1a was deleted using Aggrecan-Cre ERT2 in early cartilage cells with a one-time tamoxifen injection. We observed the absence of lineage progression of chondrocyte-derived bone cells to form osteoblasts and osteocytes in metaphyses. Furthermore, we demonstrated the key contribution of growth plate chondrocytes and articular chondrocytes, not only for long bone growth, but also for bone remodeling. In contrast, deleting Bmpr1a in early osteoblasts with 3.6 Col 1-Cre had little impact on skeletal shape and size except for a sharp increase in osteoblasts and osteocytes, leading to a profound increase in bone volume. We conclude that chondrogenesis and osteogenesis are one continuous developmental and lineage-defined biological process, in which Bmpr1a signaling in chondrocytes is necessary for the formation of a pool or niche of osteoprogenitors that then contributes in a major way to overall bone formation and growth.

SUBMITTER: Jing Y

PROVIDER: S-EPMC5577112 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process.

Jing Yan Y Jing Junjun J Ye Ling L Liu Xiaohua X Harris Stephen E SE Hinton Robert J RJ Feng Jian Q JQ

Scientific reports 20170830 1

Although chondrogenesis and osteogenesis are considered as two separate processes during endochondral bone formation after birth, recent studies have demonstrated the direct cell transformation from chondrocytes into bone cells in postnatal bone growth. Here we use cell lineage tracing and multiple in vivo approaches to study the role of Bmpr1a in endochondrogenesis. Our data showed profound changes in skeletal shape, size and structure when Bmpr1a was deleted using Aggrecan-Cre <sup>ERT2</sup> ...[more]

PMID: 28855706

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Project description:Osteoarthritis (OA), also known as degenerative arthritis, affects millions of people all over the world. OA occurs when the cartilage wears down over time, which is a worldwide complaint. The aim of this study was to screen and verify hub genes involved in developmental chondrogenesis as well as to explore potential molecular mechanisms.The expression profiles of GSE51812 were downloaded from the Gene Expression Omnibus (GEO) database, which contained 9 samples, including 6-week pre-chondrocytes (PC, 6 independent specimens) and 17-week fetal periarticular resting chondrocytes (RC, 3 independent specimens). The raw data were integrated to obtain differentially expressed genes (DEGs) and were further analyzed with bioinformatics analysis. The Gene Ontology (GO) and pathway enrichment of DEGs were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID). The protein-protein interaction (PPI) networks of the DEGs were constructed based on data from the search tool for the retrieval of interacting genes (STRING) database. An intersection figure was provided to show the relationship between the DEGs identified in this study and genes from any existed related studies.A total of 9486 DEGs, including 4821 upregulated genes and 4665 downregulated genes were observed. The top 30 developmental chondrogenesis associated genes were identified, including matrix metalloproteinase (MMP)1, MMP3, MMP13, prostaglandin-endoperoxide synthase 2 (PTGS2), and so on. The majority of DEGs, including PTGS2, CCL20, CHI3L1, LIF, CXCL8, and CXCL12 were intensively enriched in immune-associated biological process terms, including inflammatory, and immune responses. Additionally, the majority of DEGs were mainly enriched in NF-kappa β (NF-kβ) signaling pathway and tumor necrosis factor (TNF) signaling pathway. The hub genes identified in STRING and Cytoscape databases included MMP1, MMP3, MMP13, PTGS2 and so on. Among the top 30 upregulated and downregulated DEGs, there were 15 genes have been reported to be associated with OA or developmental chondrogenesis.This large scale gene expression study observed genes associated with human developmental chondrogenesis and their relative GO function, which may offer opportunities for the research for cartilage tissue engineering and novel insights into the prevention of OA in the near future.

Dataset Information

Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process.

Publications

Chondrogenesis and osteogenesis are one continuous developmental and lineage defined biological process.

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