Ameliorative effects of undifferentiated and differentiated BM-MSCs in MIA-induced osteoarthritic Wistar rats: roles of NF-κB and MMPs signaling pathways

未分化和分化 BM-MSCs 对 MIA 诱发的骨关节炎 Wistar 大鼠的改善作用:NF-κB 和 MMPs 信号通路的作用

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作者:Ablaa S Saleh, Mohammed Abdel-Gabbar, Hala Gabr, Anwar Shams, Shadi Tamur, Emad A Mahdi, Osama M Ahmed

Conclusions

It is possible to conclude from these results that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA, which may be mediated via inhibitory effects on oxidative stress, MMPs and inflammation through suppressing the NF-κB pathway. In osteoarthritis, using CD-MSCs as a treatment is more beneficial therapeutically than using BM-MSCs.

Methods

Male Wistar rats were injected three times with MIA (1 mg)/100 µL isotonic saline to induce osteoarthritis in the ankle joint of the right hind leg. Following the MIA injection, the osteoarthritic rats were given weekly treatments of 1 × 106 BM-MSCs and CD-MSCs into the tail vein for three weeks.

Results

The obtained results showed that in osteoarthritic rats, BM-MSCs and CD-MSCs dramatically decreased ankle diameter measurements, decreased oxidized glutathione (GSSG) level, and boosted glutathione peroxidase (GPx) and glutathione reductase (GR) activities. Additionally, in rats with MIA-induced OA, BM-MSCs and CD-MSCs dramatically boosted interleukin-10 (IL-10) serum levels while considerably decreasing serum anticitrullinated protein antibodies (ACPA), tumour necrosis factor-α (TNF-α), and interleukin-17 (IL-17) levels as well as ankle transforming growth factor-β1 (TGF-β1) expression. Analysis of histology, immunohistochemistry, and western blots in osteoarthritic joints showed that cartilage breakdown and joint inflammation gradually decreased over time. Conclusions: It is possible to conclude from these results that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA, which may be mediated via inhibitory effects on oxidative stress, MMPs and inflammation through suppressing the NF-κB pathway. In osteoarthritis, using CD-MSCs as a treatment is more beneficial therapeutically than using BM-MSCs.

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