Lumbar intervertebral disc mRNA sequencing identifies the regulatory pathway in patients with disc herniation and spondylolisthesis.

摘要: Abstract Lumbar degenerative disc disease (DDD) is a multifaceted progressive condition and often accompanied by herniation (DH) and/or spondylolisthesis (DS). Given the high prevalence of (up to 20% according some estimates) costs associated with its care, there need explore novel therapies such as regenerative medicine. Exploring these first warrants investigation molecular pathways underlying disorders. Here, we show results from next generation RNA sequencing (RNA-seq) on mRNA isolated 10 human nucleus pulposus (NP) samples lumbar degenerated discs (DH DS; n = 5 for each tissue) other musculoskeletal tissues (Bone, cartilage, growth plate, muscle; n = 7 tissue). Pathway network analyses based gene ontology (GO) terms were used identify biological functions differentially expressed mRNAs. A total 701 genes found be significantly upregulated in NP tissue compared tissues. These mRNAs primarily involved DNA damage, immunity G1/S transition mitotic cell cycle. Interestingly, DH-specific signaling showed major chemotactic (e.g., CXCL10, CXCL11, IL1RL2 IL6) matrix-degrading pathway MMP16, ADAMTSL1, 5, 8, 12, 15), while DS-specific those adhesion CDH1, EPHA1 EFNA2) inflammatory cytokines CD19, CXCL5, CCL24, 25 XCL2). Our findings provide new leads therapeutic drug discovery that would permit optimization medical or pharmacological intervention cases DDD.