Activated Growth Factor (AGF) as a Superior Biological Therapy for Osteoarthritis: Comparative Efficacy in Modulating Cartilage Degeneration and Inflammation in vivo.

Abstract

Purpose: This study aimed to explore the effect of activated growth factor (AGF) in anabolic-catabolic regulation pathway in an experimental osteoarthritis (OA) rat model. This investigation was predicated on the critical need for a disease-modifying osteoarthritis drug, seeking to determine if AGF could restore chondral homeostasis by reversing the catabolic-dominant state that defines OA pathology. This is the first study to compare AGF with platelet-rich plasma (PRP) and diclofenac sodium in vivo.

Methods: Fifty-six male Wistar rats were randomly allocated into seven groups (n = 8 per group); normal control (NC), negative control (OA induced, saline-treated), positive control with platelet-rich plasma (PRP) (OA induced + PRP), positive control diclofenac (OA induced + Diclofenac sodium), AGF 0.1 ng/mL (OA induced + AGF with TGF-β at 0.1 ng/mL), AGF 1 ng/mL (OA induced + AGF with TGF-β at 1 ng/mL), AGF 10 ng/mL (OA induced + AGF with TGF-β at 10 ng/mL). Cartilage anabolic-catabolic status was assessed by measuring matrix metalloproteinases (MMP-1, MMP-13), a-disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), SMAD3, aggrecan, and collagen type II (Col2) expression via ELISA and Western blot. Key inflammatory mediators (TNF-α, IL-1β, NF-κB) and histopathological changes were also evaluated.

Results: AGF treatment demonstrated superior efficacy in modulating anabolic-catabolic balance compared to OA controls and PRP. AGF dose-dependently and significantly decreased MMP-1, MMP-13, and ADAMTS-4 levels. Conversely, AGF significantly increased SMAD3 phosphorylation, aggrecan synthesis, and Col2 expression, surpassing the effects of PRP. The 10 ng/mL AGF group showed the most pronounced chondroprotective and anabolic effects, often restoring parameters towards normal levels. Furthermore, AGF significantly reduced TNF-α, IL-1β, and NF-κB levels, and diminished inflammatory cell infiltration, with the 10 ng/mL dose being comparable or superior to Diclofenac in these anti-inflammatory/anti-catabolic effects. PRP showed moderate benefits, generally less than AGF formulations.

Conclusion: Platelet-derived AGF, as an advanced mode of PRP, effectively regulates the anabolic-catabolic processes in OA cartilage. It achieved this by significantly inhibiting key catabolic enzymes and pro-inflammatory mediators, while concurrently promoting crucial anabolic signaling pathways and extracellular matrix synthesis. These findings highlight AGF's substantial therapeutic potential as a disease-modifying biological agent for OA.