# Three-Month Administration of PB125 Modifies Histopathology, Redox Homeostasis, and Mobility in the Hartley Guinea Pig Model of Primary Osteoarthritis

## TL;DR

This study explores how PB125 affects OA development in guinea pigs, showing sex-dependent effects on cartilage and mobility.

## Contribution

The study reveals sex-specific molecular and functional effects of PB125 in a primary OA model.

## Key findings

- PB125 reduced OA scores in female guinea pigs' distal femurs and altered redox-related gene expression.
- Female PB125-treated animals showed decreased mobility metrics, while males showed changes in voluntary mobility.
- Results suggest PB125 may influence OA initiation through sex-dependent mechanisms.

## Abstract

The pathogenesis of primary osteoarthritis (OA) is complex and multifactorial. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor that regulates hundreds of genes involved with cytoprotection. The role of Nrf2 in OA remains undefined. We utilized the Hartley guinea pig model of primary OA to investigate the role of a purported Nrf2 activator, PB125, in delaying the onset of knee OA. We hypothesized that three months of daily PB125 supplementation would modify structural, molecular, and in vivo functional outcomes characteristic of disease. Fifty-six 2-month-old animals (equal sexes) were treated orally with PB125 or vehicle control for 3 months; animals were sacrificed at 5 months, which represents mild OA and early disease. Outcome measures included knee histopathology, mRNA expression, immunohistochemistry, and in vivo mobility. Notably, PB125 treatment had differing effects in males and females. Female PB125-treated animals had significantly decreased distal femur OA scores, accompanied by differential gene and protein expression patterns in articular cartilage for markers related to redox homeostasis; decreases in one compulsory mobility metric were also seen. In contrast, males demonstrated a statistical difference in voluntary mobility patterns. In summary, PB125 may modify the molecular mechanisms involved in the initiation of early OA in a potential sex-dependent fashion.