Unravelling the role of dipeptidyl peptidases-8/9 (DPP-8/9) in inflammatory osteoporosis: a comprehensive study investigating chrysin as a potential anti-osteoporotic agent

• Published in: Journal of pharmacy and pharmacology 2024-09
• Main Authors: Ahmad, Syed Sufian, Ahmed, Faraha, Alam, Mohd Mumtaz, Ahmad, Sayeed, Khan, Mohammad Ahmed
• Format: Article
• Language: English
• ISSN: 0022-3573; 2042-7158; 2042-7158
• DOI: 10.1093/jpp/rgae109

This study aimed to investigate the role of dipeptidyl peptidase-8 and 9 (DPP-8/9) enzymes in inflammatory bone loss using a 4-vinylcyclohexene diepoxide (VCD)-induced model in Wistar rats. Additionally, we evaluated the therapeutic potential of inhibiting these enzymes with the flavonoid chrysin. Inflammatory osteoporosis was induced by administering VCD that elevated interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) levels. DPP-8/9 enzyme expression and various bone markers were assayed using serum. Further analysis included bone microarchitecture, histology, and immunohistochemistry. Additionally, chrysin's potential to inhibit DPP-8/9 and mitigate VCD-induced inflammatory bone loss was also evaluated. VCD administration in rats caused ovotoxicity that increased IL-6 and TNF-α levels, resulting in significant bone loss. Serum analysis revealed elevated bone resorption markers and DPP-8/9 enzyme levels. Inhibiting DPP-8/9 with 1G244 reversed these effects, confirmed by histology, immunohistochemistry, and micro-CT scans. Moreover, chrysin significantly reduced DPP-8/9 levels compared with the untreated group, improved bone markers, and lower inflammatory cytokines, indicating reduced osteoclastogenesis. This study highlights the role of DPP-8/9 in inflammation-induced osteoporosis. Following inhibition of DPP-8/9, we observed improved bone markers with preservation of trabecular bone mineral density in rats. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, suggesting its viability for future therapeutic interventions in DPP-8/9-related inflammatory diseases.