TABLE 1.
Summary of genes and signaling pathways that play an important role in intervertebral disc development.
| Gene | Model | Development | Degeneration | Citation |
|---|---|---|---|---|
| ApoE | KO | Decreased GAG in NP cells | Early IVD degeneration | Zhang et al. (2013) |
| Bapx1 | KO | Skeletal dysplasia in the vertebral column; Struncated axial skeleton | Chatterjee et al. (2014) | |
| Bgn | KO | Accelerated IVD degeneration | (Furukawa et al., 2009) | |
| Casp3 | KO | Smaller IVDs and body size, higher IVD cell density | Accelerated age-related IVD degeneration | (Ohnishi et al., 2019) |
| CCN2 | cKO | Disrupted IVD formation | Accelerated age-related degeneration | (Bedore et al., 2013) |
| Col1a1 | KO | Mechanical properties of discs were significantly inferior | (Sarver and Elliott, 2004) | |
| Col2a1 | KO | Less GAG in IVD | Mild disc degeneration | (Sahlman et al., 2001) |
| Col9a1 | KO | Accelerated IVD degeneration, NP shrinkage, AF fissures | (Kimura et al., 1996) | |
| Ext1 | cKO | Missing IVDs and aberrant organization | Mundy et al. (2011) | |
| Foxa1/Foxa2 | cKO | Severe NP deformation, missing tail IVD | Maier et al. (2013) | |
| GDF-5 | KO | Loss of normal AF structure, disorganized NP, decreased PG content | (Li et al., 2004) | |
| Has2 | KO | Changes in NP cellular organization, early mortality | Roughley et al. (2011) | |
| HIP-1α | cKO | Accelerated IVD degeneration | (Meng et al., 2018) | |
| IFT80 | cKO | Disrupted structure, cilia loss | Li et al. (2020) | |
| Ihh | cKO | Enlarged NP, no AF | Maeda et al. (2007) | |
| IL-1 | KO | Increased degeneration in AF | Gorth et al. (2019) | |
| Jun | cKO | NP hypocellularity, defective IVD formation | Behrens et al. (2003) | |
| NF-κB | KO | Increased PG synthesis and reduced disc cellularity loss | Nasto et al. (2012) | |
| Pax1 | KO | IVD absent | Wallin et al. (1994) | |
| Progranulin | KO | Early onset of IVD degeneration | Zhao et al. (2015) | |
| Runx2 | cKO | Vacuolated cells in NP | (Liao et al., 2019) | |
| Sd | KO | Absence of NP and reduced vertebrae number | Lane and Birkenmeier (1993); Alfred et al. (1997) | |
| Shh | cKO | Absence of NP | Choi and Harfe (2011) | |
| Skt | KO | Dislocation of NP and kinky tail | Semba et al. (2006) | |
| Smo | cKO | Aberrant NP formation | Choi and Harfe (2011) | |
| Sox5/Sox6 | KO | Absence of NP | Smits and Lefebvre (2003) | |
| Sox9 | cKO | AF and NP ECM remodeling, progressive IVD degeneration | Tsingas et al. (2020) | |
| TSC-1 | cKO | NP and AF absent | Yang et al. (2017) | |
| Tgfbr2 | cKO | Incomplete or missing IVD | Loss of matrix in inner AF, IVD maintenance defects | Baffi et al. (2004); Jin (2011) |
| Wnt/βcat | cKO | Severe AF deterioration | Increased IVD degeneration | Kondo et al. (2011); Silva and Holguin (2020) |
AF, annulus fibrosus; NP, nucleus pulposus; GAG, glycosaminoglycan; IVD, intervertebral disc; ECM, extracellular matrix; PG, proteoglycan; KO, knockout; cKO, conditional knockout.