الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
. Osteoarthritis (OA) is a chronic inflammatory disease that causes joint swelling, pain, and bone and cartilage destruction leading to functional disability. MIA-induced osteoarthritis is a model of chronic osteoarthritis with features that resemble animal OA in many respects, and is one of the best experimental models for detection and evaluation of compounds with anti-inflammatory activity.
So far there are no drugs available to guarantee a complete cure and the possibility of recurrence from OA, and that all of the therapy is aimed at slowing the progression of the disease and decreasing the clinical signs. Regenerative medicine represents an interesting alternative for treating OA.
The present study has been conducted to evaluate the therapeutic effect of bone marrow mesenchymal stem cells, platelet-rich plasma, and hyaluronic acid as well as the concurrent administration of BMMSCs and PRP, and BMMSCs and HA on Monosodium iodoacetate adjuvant (MIA) induced osteoarthritis in experimental rats.
This study included 70 adult male Wistar rats which were divided into seven groups (ten animals for each) designed as follows:
group 1 (Normal group): The rats within this group were weekly injected with the equivalent volume of the saline (50 μL) in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after saline injection
group 2 (Osteoarthritic control group): This group consists of osteoarthritic rats that were weekly received equivalent volume of the saline (50 μL) in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after MIA injection.
group 3 (Osteoarthritic group treated with BMMSCs) This group consists of osteoarthritic rats that were weekly injected with50 μL PBS (1×106 normal BMMSCs cells) in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after MIA injection
group 4 (Osteoarthritic group treated with HA) This group consists of osteoarthritic rats that were weekly injected with 50 μL of 15mg/ml HA in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after MIA injection
group 5 (Osteoarthritic group treated with BMMSCs plus HA) This group consists of osteoarthritic rats that were weekly treated with IA injection of 50 μL PBS (1×106 normal BMMSCs cells), followed by IA injection 50 μL of HA in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after MIA injection.
group 6 (Osteoarthritic group treated with PRP) This group consists of osteoarthritic rats that were weekly injected with 50 μL of prp in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after MIA injection.
group 7 (Osteoarthritic group treated with BMMSCs plus PRP) This group consists of osteoarthritic rats that were weekly treated with IA injection of 50 μL PBS (1×106 normal BMMSCs cells), followed by an IA injection 50 μL of prp in the tibiotarsal joint of the right hind paw at 14, 21, and 28 days after MIA injection.
Saline and all treatments were applied by IA injection into the right ankle.
After 42 days, the animals were anesthetized with diethyl ether and blood samples were collected from jugular vein. After decapitation and dissection, tissue samples (ankle joint) were rapidly excised for physiological and biochemical assays as well as for histopathological studies. MIA-administered group (osteoarthritic control) was compared with the normal one, while the osteoarthritic rats treated with BMMSCs, PRP, HA, BMMSCs plus PRP and BMMSCs plus HA were compared with the osteoarthritic control group.
Results showed that MIA administration caused a marked elevation in paw edema of the osteoarthritic rats as indicated by increase in right hind leg circumference at paw region, MRI and increase ankle measurement in comparison with the normal rats. This parameter was decreased significantly as a result of all treatments which suggest the effectiveness of these treatments on treating OA.
The TLC hematological alterations were evidenced by an obvious leukocytosis counts in the osteoarthritic control animals. It was found that the five treatments declined markedly the TLC near to their normal levels, indicating the anti-inflammatory effect of the treatments in MIA-induced osteoarthritis.
Concerning oxidative stress and antioxidant defense system, the serum LPO was significantly elevated in MIA-induced osteoarthritic rats while the GSH content and the activities of antioxidant enzyme GST were significantly decreased. The treatment with PRP, HA and/or BMMSCs markedly decreased the elevated LPO. On the other hand, the declined GSH content and GST activities are replenished successfully by PRP, HA and/or BMMSCs supplementation. These results refer that the five treatments play an important role in preventing and treating the MIA-induced osteoarthritis through inhibition of the oxidative stress and enhancement of antioxidant defense system.
In the present study, in the osteoarthritic control group, the levels of inflammatory cytokines including IL-17 and TNF-α beside the mRNA expression level of MMP-13 were significantly increased. On the other hand, the level of anti-inflammatory cytokine IL-4 was extremely down-regulated. The treatment of the osteoarthritic rats with PRP, HA and/or BMMSCs potentially decreased the elevated pro-inflammatory and inflammatory mediators (IL-17, TNF-α) levels. Also, the anti-inflammatory (IL-4) cytokine were ameliorated significantly by PRP, HA and/or BMMSCs supplementation.
Histopathologically, the former results of the biochemical indices are supported by the histopathological examination of the ankle joint sections. The PRP, HA and/or BMMSCs treated osteoarthritic rats showed an obvious reduction with varying degrees in the extent of inflammatory cells infiltration in the fibrous joint capsules, decrease cartilage degradation, synovitis and bone erosion when compared with the arthritic control group.
This is consistent with the reduction of the proinflammatory and inflammatory cytokines and enhancement of the anti-inflammatory status as a result of the treatments.
Conclusionally, the results of the present study suggest that BMMSCs, HA and PRP have potent anti-inflammatory, anti-oxidant and anti-arthritic effects in MIA-induced osteoarthritis in Wistar rats. BMMSCs and prp concurrently administered may have less powerful preventive and therapeutic action against MIA-induced osteoarthritis in Wistar rats. BMMSCs and HA concurrently administered may have powerful preventive and therapeutic action against MIA-induced arthritis in Wistar rats which suggests that there is somehow synergism between both of them together better than each treatment alone.