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Transcriptomic alterations in hypertrophy of the ligamentum flavum: interactions of Rho GTPases, RTK, PIK3, and FGF

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Abstract

Purpose

To analyze the differential transcriptome expression in hypertrophic ligaments flavum (HLF) compared to normal ligaments.

Methods

A case–control study was conducted that included 15 patients with hypertrophy of LF and 15 controls. Samples of LF were obtained through a lumbar laminectomy and analyzed by DNA microarrays and histology. The dysregulated biological processes, signaling pathways, and pathological markers in the HLF were identified using bioinformatics tools.

Results

The HLF had notable histological alterations, including hyalinosis, leukocyte infiltration, and disarrangement of collagen fibers. Transcriptomic analysis showed that up-regulated genes were associated with the signaling pathways of Rho GTPases, receptor tyrosine kinases (RTK), fibroblast growth factors (FGF), WNT, vascular endothelial growth factor, phosphoinositide 3-kinase (PIK3), mitogen-activated protein kinases, and immune system. The genes PIK3R1, RHOA, RPS27A, CDC42, VAV1, and FGF5, 9, 18, and 19 were highlighted as crucial markers in HLF. The down-expressed genes in the HLF had associations with the metabolism of RNA and proteins.

Conclusion

Our results suggest that abnormal processes in hypertrophied LF are mediated by the interaction of the Rho GTPase, RTK, and PI3K pathways, which have not been previously described in the HLF, but for which there are currently therapeutic proposals. More studies are required to confirm the therapeutic potential of the pathways and mediators described in our results.

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Acknowledgements

The authors thank Lorena Chávez, José Luis Santillán, Simón Guzmán, and Jorge Ramírez for the microarray analysis and Mayra Torres Quintana for her support in processing the tissues for histology.

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Authors and Affiliations

  1. Laboratorio PABIOM, Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, 31125, Chihuahua, Chihuahua, México

    Fernando Guevara-Villazón, César Pacheco-Tena, Antonio Anchondo-López & Susana Aideé González-Chávez

  2. Neuroteam CUU, Hospital Ángeles Chihuahua, Chihuahua, México

    Fernando Guevara-Villazón, Luis Alberto Ordoñez-Solorio, Benjamín Contreras Martínez & Arturo Muñoz-Cobos

  3. Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, Chihuahua, México

    Arturo Luévano-González

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  1. Fernando Guevara-Villazón
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  2. César Pacheco-Tena
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Correspondence to César Pacheco-Tena or Susana Aideé González-Chávez.

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Guevara-Villazón, F., Pacheco-Tena, C., Anchondo-López, A. et al. Transcriptomic alterations in hypertrophy of the ligamentum flavum: interactions of Rho GTPases, RTK, PIK3, and FGF. Eur Spine J 32, 1901–1910 (2023). https://doi.org/10.1007/s00586-023-07721-5

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