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Identification of novel genes associated with fracture healing in osteoporosis induced by Krm2 overexpression or Lrp5 deficiency.

ABSTRACT: The aim of the present study was to screen potential key genes associated with osteoporotic fracture healing. The microarray data from the Gene Expression Omnibus database accession number GSE51686, were downloaded and used to identify differentially expressed genes (DEGs) in fracture callus tissue samples obtained from the femora of type I collagen (Col1a1)?kringle containing transmembrane protein 2 (Krm2) mice and low density lipoprotein receptor?related protein 5?/? (Lrp5?/?) transgenic mice of osteoporosis compared with those in wild?type (WT) mice. Enrichment analysis was performed to reveal the DEG function. In addition, protein?protein interactions (PPIs) of DEGs were analyzed using the Search Tool for the Retrieval of Interacting Genes database. The coexpression associations between hub genes in the PPI network were investigated, and a coexpression network was constructed. A total of 841 DEGs (335 upregulated and 506 downregulated) were identified in the Col1a1?Krm2 vs. the WT group, and 50 DEGs (16 upregulated and 34 downregulated) were identified in the Lrp5?/? vs. the WT group. The DEGs in Col1a1?Krm2 mice were primarily associated with immunity and cell adhesion (GO: 0007155) functions. By contrast, the DEGs in Lrp5?/? mice were significantly associated with muscle system process (GO: 0003012) and regulation of transcription (GO: 0006355). In addition, a series of DEGs demonstrated a higher score in the PPI network, and were observed to be coexpressed in the coexpression network, and included thrombospondin 2 (Thbs2), syndecan 2 (Sdc2), FK506 binding protein 10 (Fkbp10), 2'?5'-oligoadneylate synthase?like protein 2 (Oasl2), interferon induced protein with tetratricopeptide repeats (Ifit) 1 and Ifit2. Thbs2 and Sdc2 were significantly correlated with extracellular matrix?receptor interactions. The results suggest that Thbs2, Sdc2, Fkbp10, Oasl2, Ifit1 and Ifit2 may serve important roles during the fracture healing process in osteoporosis. In addition, this is the first study to demonstrate that Sdc2, Fkbp10, Oasl2, Ifit1 and Ifit2 may be associated with osteoporotic fracture healing.

SUBMITTER: Gao F

PROVIDER: S-EPMC5436207 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Identification of novel genes associated with fracture healing in osteoporosis induced by Krm2 overexpression or Lrp5 deficiency.

Gao Feng F Xu Feng F Wu Dankai D Cheng Jieping J Xia Peng P

Molecular medicine reports 20170503 6

The aim of the present study was to screen potential key genes associated with osteoporotic fracture healing. The microarray data from the Gene Expression Omnibus database accession number GSE51686, were downloaded and used to identify differentially expressed genes (DEGs) in fracture callus tissue samples obtained from the femora of type I collagen (Col1a1)‑kringle containing transmembrane protein 2 (Krm2) mice and low density lipoprotein receptor‑related protein 5‑/‑ (Lrp5‑/‑) transgenic mice ...[more]

PMID: 28487939

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Project description:Fracture healing requires controlled expression of thousands of genes. Only a small fraction of these genes have been isolated and fewer yet have been shown to play a direct role in fracture healing. The purpose of this study was threefold: (1) to develop a reproducible open femur model of fracture healing that produces consistent fracture calluses for subsequent RNA extraction, (2) to use this model to determine temporal expression patterns of known and unknown genes using DNA microarray expression profiling, and (3) to identify and validate novel gene expression in fracture healing. In the initial arm of the study, a total of 56 wild-type C57BL/6 mice were used. An open, stabilized diaphyseal femur fracture was created. Animals were killed at 1, 5, 7, 10, 14, 21, and 35 days after surgery and the femurs were harvested for analysis. At each time point, fractures were radiographed and sectioned for histologic analyses. Tissue from fracture callus at all stages following fracture yielded reproducibly large amounts of mRNA. Expression profiling revealed that genes cluster by function in a manner similar to the histologic stages of fracture healing. Based on the expression profiling of fracture tissue, temporal expression patterns of several genes known to be involved in fracture healing were verified. Novel expression of multiple genes in fracture callous tissue was also revealed including leptin and leptin receptor. In order to test whether leptin signaling is required for fracture repair, mice deficient in leptin or its receptor were fractured using the same model. Fracture calluses of mice deficient in both leptin or leptin receptor are larger than wild-type mice fractures, likely due to a delay in mineralization, revealing a previously unrecognized role of leptin signaling in fracture healing. This novel model of murine fracture repair is useful in examining both global changes in gene expression as well as individual signaling pathways, which can be used to identify specific molecular mechanisms of fracture healing.

Dataset Information

Identification of novel genes associated with fracture healing in osteoporosis induced by Krm2 overexpression or Lrp5 deficiency.

Publications

Identification of novel genes associated with fracture healing in osteoporosis induced by Krm2 overexpression or Lrp5 deficiency.

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