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Abstract

Objectives: Rheumatoid arthritis (RA) and osteoporosis are chronic diseases characterized by fibroblastic proliferation, infiltration of the synovial lining by inflammatory cells and increase bone resorption respectively. Sphingosine -1-phosphate (S1P) receptor analogues plays unique pathogenic mechanistic role which can be beneficial to reduce the side effects and improve the efficiency for the treatment of rheumatoid arthritis and osteoporosis.

Methods: Osteoporosis and rheumatoid arthritis are induced by ovariectomy and single injection of CFA in rats. On 16th, 23rd, 30th, 37th day after ovariectomy, mechanical allodynia, thermal hyperalgesia, paw volume, joint stiffness and mobility were observed. On 37th day animal sacrificed for rheumatoid factor, calcium and phosphate and haemoglobin count in serum were determined.

Results: Ovariectomy and CFA significantly induced symptoms of osteoporosis and RA in rats like joint stiffness, decrease in , paw oedema, mechanical allodynia and thermal hyperalgesia. Increase in rheumatoid factor and decline of haemoglobin, calcium and phosphate count was also observed after sacrificing the animals. FTY720 (0.1 and 0.3 mg/kg), methotrexate (0.3 mg/kg) and diclofenac (5 mg/kg) attenuated all the behavioural and haematological parameters alone and/or combination as well as alone.

Conclusion: In the present set of experiments FTY720 has shown significant anti-arthritic and anti-osteoporotic effect in rats. Further, when FTY720 low dose was combined with standard drugs like methotrexate and diclofenac showed the synergistic effect.

Keywords: Complete freund’s adjuvant; FTY720; Osteoporosis; Ovariectomy; Rheumatoid arthritis