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. 2022 Nov 3;23(21):13479.
doi: 10.3390/ijms232113479.

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review

Vadim A Byvaltsev  1   2 , Andrei A Kalinin  1   2 , Phillip A Hernandez  3 , Valerii V Shepelev  1 , Yurii Y Pestryakov  1 , Marat A Aliyev  4 , Morgan B Giers  3
Affiliations

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review

Vadim A Byvaltsev et al. Int J Mol Sci. .

Abstract

Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/β-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.

Keywords: congenital disease; degenerative disease; genetics; molecular mechanisms; spinal stenosis; systematic review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Search strategy and selection of literature for inclusion in the systematic review.
Figure 2
Figure 2
Schematic representation of the spinal motion segment: 1—nucleus pulposus; 2—annulus fibrosus; 3—posterior longitudinal ligament; 4—spinal cord; 5—ligamentum flavum; 6—facet joints.
Figure 3
Figure 3
Mechanisms leading to spinal canal stenosis: (A)—ossification of the posterior longitudinal ligament spinal stenosis; (B)—ossification of the ligamentum flavum; (C)—osteoarthritis and hypertrophy of the facet joints leading to stenosis of the spinal canal; (D)—herniated disc.
Figure 4
Figure 4
BMP/TGF-β signaling pathway for the formation of osteoblastogenesis.
Figure 5
Figure 5
Canonical Wnt/β-catenin signaling pathway.
See this image and copyright information in PMC

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