Table I.
Most upregulated upstream regulators of imatinib using the ingenuity pathway analysis system.
| Gene symbol | Gene name | P-value of overlap | Regulates | General functions | Function related to bone biology |
|---|---|---|---|---|---|
| GLDN | Gliomedin | 7,54E-04 | Voltage-gated sodium channel, SPTBN4, ANK3, NFASC | Involved in the formation of the nodes of Ranvier along myelinated axons. | N/A |
| FREM2 | FRAS1 related extracellular matrix protein 2 | 7,54E-04 | FREM1, FRAS1, FREM2 | Extracellular matrix protein required for maintenance of the integrity of skin and renal epithelium. Also required for epidermal adhesion. | N/A |
| NRCAM | Neuronal cell adhesion molecule | 7,54E-04 | Voltage-gated sodium channel, NFASC, SPTBN4, ANK3, NRCAM, GLDN, neurotrophin | Ankyrin-binding protein involved in neuron-neuron cell adhesion. Role in the molecular assembly of the nodes of Ranvier. | N/A |
| GRIP1 | Glutamate receptor interacting protein 1 | 7,54E-04 | FRAS1, GRIA2, NR1I3, GRIP1, FREM2, FREM1, ESRRA, TFF1, HNF4A, ESR1, MEF2C, kinesin, ampa receptor | May be a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons. | N/A |
| VLDLR | Very low density lipoprotein receptor | 7,54E-04 | Cholesterol, triacylglycerol, DAB1, Ptk, DNA endogenous promoter, phospholipid, fatty acid, RAC1, LPL, SERPINE1, glycoprotein, RNA polymerase II, very low density lipoprotein | Binds VLDL and transport it into the cells by receptor-mediated endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Important in VLDL-triglyceride metabolism and the reelin signaling pathway. | Support osteoblast differentiation and proliferation (21,22). Indirectly regulates bone mineral density and remodeling through cholesterol level (23). |
Data on the function of the most upregulated upstream regulators in bone biology were collected from the literature. Gene symbols, names and primary functions were listed to standard Genecards (http://www.genecards.org). P-values of overlap were calculated using Fisher's exact test and P<0.01 was considered to indicate a statistically significant difference.