Anti-senescence and Anti-inflammatory Effects of the C-terminal Moiety of PTHrP Peptides in OA Osteoblasts.
J Gerontol A Biol Sci Med Sci
; 72(5): 624-631, 2017 May 01.
Article
en En
| MEDLINE
| ID: mdl-27271252
ABSTRACT
Osteoarthritis (OA) is characterized by degenerative changes in the whole joint leading to physical disability in the elderly population. This condition is associated with altered bone metabolism in subchondral areas suggesting that therapeutic strategies aimed at modifying bone cell metabolism may be of interest. We have investigated the effects of several parathyroid hormone-related protein (PTHrP)-derived peptides (1-37) (N-terminal), (107-111) and (107-139) (C-terminal) on senescence features induced by inflammatory stress in human OA osteoblasts. Incubation of these primary cells with interleukin(IL)-1ß led to an increased expression of senescence markers senescence-associated-ß-galactosidase activity, γH2AX foci, p16, p21, p53, and caveolin-1. PTHrP (107-111) and PTHrP (107-139) significantly reduced all these parameters. Both peptides decreased the production of IL-6 and prostaglandin E2 which was the consequence of cyclo-oxygenase-2 downregulation. PTHrP (107-139) also reduced tumor necrosis factor-α release. These anti-inflammatory effects would be related to the reduction of nuclear factor-κB activation by both peptides and activator protein-1 by PTHrP (107-139). The three PTHrP peptides favored osteoblastic function although the C-terminal domain of PTHrP was more efficient than its N-terminal domain. Our data support an anti-senescence and anti-inflammatory role for the C-terminal moiety of PTHrP with potential applications in chronic inflammatory conditions such as OA.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Osteoartritis
/
Senescencia Celular
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Proteína Relacionada con la Hormona Paratiroidea
Límite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
J Gerontol A Biol Sci Med Sci
Asunto de la revista:
GERIATRIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
España