PARP-1 prevents osteoarthritis pathogenesis by inhibiting apoptosis in chondrocytes: an animal study.

BACKGROUND

Osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage breakdown, synovial inflammation, and subchondral bone changes. Chondrocyte apoptosis is a key contributor to cartilage degradation in OA. Poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme involved in DNA repair and apoptosis regulation, is associated with various degenerative diseases. However, its role in OA pathogenesis remains unclear. Therefore, we aimed to investigate the role of PARP-1 in OA pathogenesis using PARP-1 knockout (KO) mice and primary chondrocytes.

METHODS

OA was induced in wild-type (WT) and PARP-1 KO mice via destabilization of the medial meniscus (DMM). Histological analysis was performed to assess cartilage degeneration, while chondrocyte apoptosis in joint tissues was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In vitro experiments were conducted using primary chondrocytes isolated from WT and PARP-1 KO mice, and PARP-1 activity was pharmacologically inhibited using 3-aminobenzamide (3-AB). Apoptosis was assessed by TUNEL staining and immunoblot analysis of cleaved PARP-1, poly(ADP-ribose), and caspase-3. The expression of anabolic and catabolic markers was also evaluated under inflammatory conditions.

RESULTS

PARP-1 KO mice exhibited significantly greater cartilage degeneration and chondrocyte apoptosis than did WT controls following DMM surgery. In vitro, PARP-1 deficiency or pharmacological inhibition significantly increased apoptosis and disrupted the balance between anabolic and catabolic factors under inflammatory conditions, thereby exacerbating cartilage degradation.

CONCLUSIONS

This study demonstrates that PARP-1 plays a protective role in preserving cartilage integrity under OA conditions. Its deficiency leads to increased apoptosis and cartilage degeneration both in vivo and in vitro. These findings highlight the regulatory role of PARP-1 in OA pathogenesis and underscore the need for further investigation into its underlying mechanisms.