Anti-senescence and Anti-inflammatory Effects of the C-terminal Moiety of PTHrP Peptides in OA Osteoblasts

作者：Platas Julia; Isabel Guillen Maria; Gomar Francisco; Angel Castejon Miguel; E**rit Pedro; Jose Alcaraz Maria

来源：Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 2017, 72(5): 624-631.

DOI：10.1093/gerona/glw100

• Parathyroid hormone-related protein (PTHrP)
• derived peptides
• Inflammation
• Senescence
• Osteoblasts
• Osteoarthritis

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)-1 beta led to an increased expression of senescence markers senescence-associated-beta-galactosidase activity, gamma H2AX 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 E-2 which was the consequence of cyclo-oxygenase-2 downregulation. PTHrP (107-139) also reduced tumor necrosis factor-alpha release. These anti-inflammatory effects would be related to the reduction of nuclear factor-kappa B 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.

• 出版日期2017-5