Circular RNA hsa_circ_0083756 promotes intervertebral disc degeneration by sponging miR-558 and regulating TREM1...

Area of Science:

• Biochemistry
• Molecular Biology
• Regenerative Medicine

Background:

• Intervertebral disc degeneration (IVDD) is a primary cause of low back pain.
• Circular RNAs (circRNAs) play significant roles in IVDD pathogenesis.
• The specific function of hsa_circ_0083756 in IVDD remains largely unknown.

Purpose of the Study:

• To investigate the role and mechanism of hsa_circ_0083756 in the development of IVDD.
• To elucidate the regulatory pathway involving hsa_circ_0083756, miR-558, and TREM1 in nucleus pulposus (NP) cells.
• To evaluate the therapeutic potential of targeting hsa_circ_0083756 for IVDD treatment.

Main Methods:

• Quantitative real-time PCR (RT-qPCR) to measure gene expression.
• In vitro assays (CCK8, flow cytometry, TUNEL) to assess NP cell proliferation and apoptosis.
• Bioinformatic analyses, dual-luciferase reporter assays, RNA immunoprecipitation (RIP), and fluorescence in situ hybridization (FISH) to confirm molecular interactions.
• An in vivo rat model of IVDD to validate therapeutic efficacy.

Main Results:

• hsa_circ_0083756 expression is upregulated in degenerative NP tissues and cells.
• Knockdown of hsa_circ_0083756 enhances NP cell proliferation and extracellular matrix (ECM) formation, while overexpression inhibits these processes.
• hsa_circ_0083756 functions as a molecular sponge for miR-558, leading to increased TREM1 expression.
• In vivo silencing of hsa_circ_0083756 effectively ameliorates IVDD in a rat model.

Conclusions:

• hsa_circ_0083756 promotes IVDD progression by modulating the miR-558/TREM1 axis.
• hsa_circ_0083756 represents a promising therapeutic target for managing intervertebral disc degeneration.