Identification of biological pathways and genes associated with neurogenic heterotopic ossification by text mining

Abstract

Background Neurogenic heterotopic ossification is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury (SCI-TBI-HO). However, the underlying mechanisms of SCI-TBI-HO have proven difficult to elucidate. The aim of the present study is to identify the most promising candidate genes and biological pathways for SCI-TBI-HO. Methods In this study, we used text mining to generate potential explanations for SCI-TBI-HO. Moreover, we employed several additional datasets, including gene expression profile data, drug data and tissue-specific gene expression data, to explore promising genes that associated with SCI-TBI-HO. Results We identified four SCI-TBI-HO-associated genes, including GDF15, LDLR, CCL2, and CLU. Finally, using enrichment analysis, we identified several pathways, including integrin signaling, insulin pathway, internalization of ErbB1, urokinase-type plasminogen activator and uPAR-mediated signaling, PDGFR-beta signaling pathway, EGF receptor (ErbB1) signaling pathway, and class I PI3K signaling events, which may be associated with SCI-TBI-HO. Conclusions These results enhance our understanding of the molecular mechanisms of SCI-TBI-HO and offer new leads for researchers and innovative therapeutic strategies.

A Systematic Review of the Neuroprotective Role and Biomarker Potential of GDF15 in Neurodegeneration

“…Another study examined mesenchymal stromal cells derived from individuals with SCI or traumatic brain injury (TBI). The authors identified increased GDF15 secretion into cell lysate, indicative of a widespread cell stress response (Zhang et al, 2020). This induction was also reported in injured rodent CNS and PNS tissue in response to cryolesion (Schober et al, 2001) and sciatic nerve crush (Wang et al, 2015) respectively.…”

Unearths IFNB1 immune infiltrates in SOP-related ossification of ligamentum flavum pathogenesis

“…The pathophysiology of OLF and SOP may be closely associated with a variety of cytokines or chemokines involved with inflammation and immunology, including NFKBIA, TNFRSF11, IL-10, and CCL2. CCL2 has been strongly linked to traumatic brain injury, where it may contribute to neurogenic heterotopic ossification, and it can also be secreted by macrophages, where it may play an important role in osteoblast development in heterotopic ossification (HO) [ 29 ]. Additionally, a number of studies have hypothesized that CCL2 was an osteoporosis and osteopenia risk factor [ 30 , 31 ].…”

The Survey of Cells Responsible for Heterotopic Ossification Development in Skeletal Muscles—Human and Mouse Models

“…Neurogenic heterotopic ossification (NHO) can occur after the spinal cord injury (SCI) or traumatic brain injury (TBI). Other clinical conditions, such as cerebral stroke, anoxia, and non-traumatic myelopathies, can also attribute to NHO [ 32 , 33 , 34 ]. The incidence of NHO in spinal cord injury (40%–50%) was reported to be higher than in traumatic brain injury patients (8%–23%).…”