Polydeoxyribonucleotide ameliorates IL-1β-induced impairment of chondrogenic differentiation in human bone...

Area of Science:

• Biomedical research
• Regenerative medicine
• Cell biology

Background:

• Osteoarthritis (OA) is a widespread degenerative joint disease.
• Polydeoxyribonucleotide (PDRN) is utilized for knee OA management.
• The specific effects of PDRN on IL-1β-induced inflammation in human bone marrow-derived mesenchymal stem cells (hBMSCs) were previously unclear.

Purpose of the Study:

• To investigate the role of PDRN in mitigating IL-1β-induced impairment of chondrogenic differentiation in hBMSCs.
• To elucidate the underlying molecular mechanisms of PDRN action in an inflammatory OA context.

Main Methods:

• Treatment of hBMSCs with PDRN and IL-1β.
• Assessment of chondrogenic differentiation using micromass culture, safranin O, and alcian blue staining.
• Analysis of chondrogenic, catabolic, and anabolic gene expression.
• Evaluation of inflammatory cytokine expression and apoptosis.
• Investigation of signaling pathways involving cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element binding protein (CREB), adenosine A2A receptor, and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB).

Main Results:

• PDRN treatment promoted chondrogenesis in hBMSCs, evidenced by larger micromass, enhanced staining, and increased chondrogenic gene expression, even under IL-1β-induced inflammation.
• PDRN suppressed inflammatory cytokine expression and reduced IL-1β-induced apoptosis in hBMSCs.
• Mechanistically, PDRN increased cAMP formation and PKA/CREB phosphorylation via adenosine A2A receptor activation, subsequently inhibiting the NF-κB signaling pathway.
• Adenosine A2A receptor activation directly reduced IL-1β-induced inflammatory cytokine expression in hBMSCs.

Conclusions:

• PDRN effectively promotes chondrogenic differentiation and exerts anti-inflammatory and anti-apoptotic effects in hBMSCs challenged with IL-1β.
• The mechanism involves the adenosine A2A receptor-mediated cAMP/PKA/CREB pathway, leading to NF-κB inhibition.
• PDRN represents a potential cell-based therapeutic agent for osteoarthritis.