POS0399 THE ION CHANNEL TRPV4 PARTICIPATES IN THE CARTILAGE PROTECTION OF IGURATIMOD ON KNEE OSTEOARTHRITIS

Background

Osteoarthritis (OA) is the leading cause of disability for bone and joint diseases. Cartilage injury is its pathological basis. There is a lack of therapeutic drugs with clear cartilage protection in clinic. Iguratimod (IGU) has cartilage protection effect in the treatment of rheumatoid arthritis, but it is not clear whether it also has cartilage protection effect on OA.

Objectives

To investigated the efficacy and mechanism of Iguratimod (IGU) on cartilage protection effect on knee osteoarthritis (OA).

Methods

Type VII collagenase was injected into the knee joint cavity of C57BL6/N rats to establish a model of CIOA (Collagenase-induced Osteoarthritis), to establish the model of osteoarthritis, followed by IGU given by intragastrium at 10mg/kg. μCT and Immunohistochemistry (IHC) were used to evaluate the structural changes of OA knee joint, the degree of destruction of knee cartilage layer and subchondral bone. IHC and qPCR were used to evaluated the expression of TPRV4 in chondrocytes of OA rats. Chondrocytes were processed by IGU at the cellular level, and the concentration of glycosaminoglycan secreted and the expression of chondrogenic differentiation factor in cells were further detected. TRPV4 ion channel inhibitor and interfering RNA technology were used to verify whether TRPV4 was involved in the effect of IGU on cartilage.

Results

It was found that IGU could change the pain sensitivity of OA model rats and effectively reduce the pain of OA rats. μCT showed that IGU could effectively inhibit the subchondral bone injury of knee joint in OA rats; Toluidine blue staining and Safranin O-Fast Green staining of rats knee joint also showed that IGU treatment could delay the degeneration of knee cartilage of rats with OA. At the cellular level, it was found by qPCR that IGU could effectively promote the expression of mRNA levels of Sox9 and Col2a, markers of chondrogenesis, in chondrocytes. Alcian blue staining also showed that IGU promoted chondrocyte secretion of glycosaminoglycan; Moreover, the results of scratch experiment also showed that IGU promoted the migration of chondrocytes. The results addressed above all indicated that IGU could promote the differentiation of chondrocytes. The expression of transient receptor point vanillin 4 (TRPV4) in OA rats chondrocytes in the treatment group of IGU was increased. We used ion channel inhibitors and interfering RNA technology to show that IGU played a role in delaying cartilage damage, promoting cartilage differentiation and migration by regulating the function of TRPV4.

Conclusion

IGU can effectively alleviate the pain of OA model rats, and exert cartilage protection by regulating TRPV4. The results offer new treatment options for osteoarthritis.

REFERENCES:

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Acknowledgements:

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Disclosure of Interests

None Declared.