Introduction:Osteoarthritis (OA) is a degenerative joint disease that can affect the
many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical
use at this time probably due to a lack of complete comprehension of the pathogenesis of the
disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated
and differentiated cells have gained much attention as they can efficiently promote tissue
repair and regeneration.Methods:To determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and
chondrogenic differentiated MSCs (CD-MSCs) can treat OA in rats, OA was induced in Wistar
rats by injecting three doses of 100 μL physiological saline containing 1 mg of MIA into rat ankle
joint of the right hind leg for three consecutive days. Following the induction, the osteoarthritic
rats were injected weekly with BM-MSCs or CD-MSCs at a dose of 1x106 cells/rat/dose for three
weeks. In addition to morphological and histological investigations of the ankle, spectrophotometric,
ELISA, and Western blot analyses were applied to detect various immunological and molecular
parameters in serum and ankle.Results:The results of the study showed that in osteoarthritic rats, BM-MSCs and CD-MSCs significantly
reduced right hind paw circumference, total leucocyte count (TLC), differential leukocyte
count (DLC) of neutrophils, monocytes, lymphocytes, and eosinophils, serum rheumatoid factor
(RF), prostaglandin E2 (PGE2) and interleukin (IL-) 1β levels, while they elevated serum
IL-10 level. Additionally, BM-MSCs and CD-MSCs markedly reduced lipid peroxides (LPO) levels
while they elevated superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities.
The monocyte chemoattractant protein-1 (MCP-1) level was significantly downregulated in
ankle joint articular tissues by treatment with BM-MSCs or CD-MSCs while nuclear factor erythroid
2-related factor 2 (Nrf2) was upregulated; CD-MSCs treatment was more effective.Conclusion:According to these findings, it can be inferred that BM-MSCs and CD-MSCs have
anti-arthritic potential in MIA-induced OA; CD-MSCs therapy is more effective than MSCs. The
ameliorative anti-arthritic effects may be mediated by suppressing inflammation and oxidative
stress through the downregulation of MCP-1 and upregulation of Nrf2. Based on the obtained results,
BM-MSCs and CD-MSCs therapies are promising new options that can be associated with
other clinical treatments to improve cartilage regeneration and joint healing. However, more preclinical
and clinical research is required to assess the benefits and safety of treating osteoarthritic
patients with BM-MSCs and CD-MSCs.