JOR Spine · Published 2025-11-30 · DOI 10.1002/jsp2.70146
ABSTRACT Background Paraspinal muscle degeneration, particularly fat infiltration, is a prominent feature of adult degenerative scoliosis (ADS), which impairs spinal stability, accelerates disease progression, and contributes to poor clinical outcomes. However, the underlying molecular mechanisms remain unclear. This study aims to investigate the role of the hsa_circ_0006156/miR‐122‐5p/PPARA regulatory axis in this process. Methods Paraspinal muscle fat infiltration was assessed by MRI in ADS patients and 40 age‐matched controls. HE staining, Oil Red O staining, and RT‐PCR were used to evaluate muscle structure and gene expression. Overexpression of hsa_circ_0006156 and inhibition of miR‐122‐5p were performed in primary multifidus muscle cells. Western blot and dual‐luciferase reporter assays were used to verify the regulatory pathway. Results Paraspinal muscle fat infiltration was significantly increased in ADS patients and showed clear asymmetry. hsa_circ_0006156 was downregulated on the concave side. Its overexpression reduced lipid accumulation, downregulated adiponectin and perilipin, and increased PPARA expression. Bioinformatics analysis and luciferase assays confirmed miR‐122‐5p as a direct target of hsa_circ_0006156, and PPARA as a downstream gene of miR‐122‐5p. Inhibiting miR‐122‐5p reduced fat accumulation and increased PPARA expression. Co‐transfection assays showed that hsa_circ_0006156 regulates lipid metabolism by sponging miR‐122‐5p and releasing its inhibition on PPARA. Conclusion Paraspinal muscles in ADS patients show marked fat infiltration with lateral asymmetry, especially on the concave side. hsa_circ_0006156 regulates lipid metabolism through the miR‐122‐5p/PPARA axis and reduces fat deposition, providing a potential molecular target for early diagnosis and intervention in ADS‐related muscle degeneration.
Abstract from DOAJ. Public domain (CC0 1.0).
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