Forsythoside B protects cartilage and subchondral bone in osteoarthritis by regulating the Nrf2/NF - κ B signaling pathway

Background: Joint diseases like osteoarthritis (OA) are common, however, there is still room for progress in the drug treatment of this disease. FTS ·B acts as an anti-inflammatory and antioxidant by blocking the NF-κB signal pathway and stimulating Nrf2, which are linked to cartilage and subchondral bone.

Purpose: At present, the main treatment of OA is symptomatic therapy, including anti-inflammatory analgesia and surgical excision, while there are fewer treatments in terms of mechanism. Our aim is to find a novel compound that acts as a therapeutic effect on OA by blocking the mechanical part of the process of OA occurrence and development.

Methods: The study employed a combination of in vitro and in vivo approaches to investigate FTS ·B effects on OA. High-density chondrocyte cultures mimicked cartilage microenvironments to assess FTS ·B's ability to prevent inflammation-induced Apoptosis and extracellular matrix (ECM) degradation. Immunofluorescence and Western blotting were used to visualize and quantify key proteins (e.g., Collagen II, MMP13) and signaling pathways (NF-κB, MAPKs, Nrf2/HO-1), while Quantitative Real-Time PCR measured osteoclast-related gene expression (NFATc1, TRAP).

Results: FTS ·B was found to protect chondrocytes in an inflammatory environment and reverse cartilage ECM degradation by activating the Nrf2/HO-1 axis and inhibiting the NF-κB and MAPKs pathways. The results of our study suggest that FTS ·B hinders the formation of osteoclasts and the breakdown of bone by blocking the NF-κB and MAPKs pathways, without impacting the Akt pathway. Moreover, treating mice with FTS ·B after DMM surgery resulted in the restoration of cartilage and prevention of subchondral bone loss.

Conclusions: Our research suggests that stimulating FTS·B pharmacologically can prevent the degradation of cartilage and subchondral bone in osteoarthritis. In contrast to prior studies that primarily targeted cartilage in the treatment of osteoarthritis, our research emphasizes the treatment of subchondral bone.

Cartilage; Forsythoside B; Nrf2; Osteoarthritis; Subchondral bone.