Rapamycin-induced hyperglycemia is associated with exacerbated age-related osteoarthritis.

ABSTRACT:

Background

The objective of this study was to determine if mechanistic target of rapamycin (mTOR) inhibition with or without AMP-activated protein kinase (AMPK) activation can protect against primary, age-related OA.

Design

Dunkin-Hartley guinea pigs develop mild primary OA pathology by 5 months of age that progresses to moderate OA by 8 months of age. At 5 months, guinea pigs served as young control (n = 3) or were fed either a control diet (n = 8), a diet enriched with the mTOR-inhibitor rapamycin (Rap, 14 ppm, n = 8), or Rap with the AMPK-activator metformin (Rap+Met, 1000 ppm, n = 8) for 12 weeks. Knee joints were evaluated by OARSI scoring, micro-computed tomography, and immunohistochemistry. Glenohumeral articular cartilage was collected for western blotting.

Result

SUBMITTER: Minton DM 

PROVIDER: S-EPMC8495984 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature