p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle.
Elife
; 92020 03 03.
Article
en En
| MEDLINE
| ID: mdl-32125276
Neck and shoulder pain, lower back pain and leg numbness are conditions that many people will encounter as years go by. This is because intervertebral discs, the padding structures that fit between the bones in the spine, degenerate with age: their cells enter a 'senescent', inactive state, and stop multiplying. A protein known as p16, an important regulator of cell growth and division, is known to accumulate in senescent cells. In fact, in mouse fat tissue, muscles or eyes, removing the cells that contain high levels of p16 delays aging-associated disorders. However, it was still unknown whether deactivating the gene that codes p16 in senescent cells could delay disc degeneration. Here, Che, Li et al. discovered that p16 is highly present in the senescent cells of severely degenerated human intervertebral discs. The cells in the nucleus pulposus, the jelly-like and most critical tissue in the intervertebral discs, were extracted and grown in the lab under conditions that replicate the early stages of damage to the spine. Drugs and genetic manipulations were then used to decrease the amount of p16 in these cells. The experiments showed that reducing the levels of p16 results in the senescent cells multiplying more and showing fewer signs of damage and aging. In addition, the discs of mice in which the gene that codes for p16 had been deleted were less prone to degeneration compared to 'normal' mice in similar conditions. Overall, the work by Che, Li et al. shows that inhibiting p16 in disc cells delays the aging process and reduces the degeneration of intervertebral discs. These findings may one day be applicable to people with intervertebral disc diseases who, for example, could potentially benefit from a gene therapy targeting the cells which produce p16.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Inhibidor p16 de la Quinasa Dependiente de Ciclina
/
Degeneración del Disco Intervertebral
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Núcleo Pulposo
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Desplazamiento del Disco Intervertebral
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Año:
2020
Tipo del documento:
Article
País de afiliación:
China