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

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.