Abstract
The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.
Highlights
84% of the population worldwide experiences low back pain in their lifetime, of which 10% develops into chronic disability, gravely affecting the quality of life and bringing huge financial burdens to families and society (Gore et al, 2012)
These results suggested the involvement of miR-1013p in Intervertebral disk degeneration (IDD) progression and the degradation of extracellular matrix (ECM) of nucleus pulposus cells (NPCs) in patients with IDD
This study clarified that miR-101-3p enhanced the effect of Bone mesenchymal stem cell (BMSC) on ECM remodeling in IDD
Summary
84% of the population worldwide experiences low back pain in their lifetime, of which 10% develops into chronic disability, gravely affecting the quality of life and bringing huge financial burdens to families and society (Gore et al, 2012). Intervertebral disk degeneration (IDD) represents an extensively identified contributor to low back pain (Risbud and Shapiro, 2014). IDD is featured by the reduction of NP and degradation of proteoglycan, Aggrecan, and collagen in the extracellular matrix (ECM), which disrupts the homeostasis of NP and shifts IVD maintenance toward degeneration and catabolism (Wang et al, 2015). The current clinical interventions for IDD mainly include conservative medication and surgery (spinal fusion or total disk replacement); these therapeutic approaches only temporarily relieve the pain symptoms, instead of providing a permanent cure (Konovalov et al, 2016; Zhu et al, 2019). Developing novel and potent therapies for patients with IDD remains an urgent issue to be solved
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