A Preliminary Study On The Regulatory Mechanism Of Osteopontin Expression In Wnt/β-catenin Signaling Pathway In Osteoarthritis

Objective:This study in order to preliminary discussion on the expression of osteopontin (OPN) whether through theβ-catenin/TCF-4 complex regulation and the related regulatory mechanism in Wnt/β-catenin signaling pathway in Osteoarthris. Thus, it can provide a new theory basis for more specific therapy promises which will be a safer and more efficient approach as a treatment targets for osteoarthritis.Methods:Primary cultures osteoarthritic and normal chondrocytes. The mRNA expression of theβ-catenin and OPN were investigated using Real Time-PCR in Osteoarthritic and normal Chondrocytes. Furthermore, we evaluated the effect of DKK-1 on OA Chondrocytes, the mRNA expression of OPN was evaluated by Real Time-PCR and the protein expression was evaluated by Western blot. Moreover, blocking TCF-4 expression was performed using small interfering RNA (siRNA) against TCF-4 in osteoarthritic chondrocytes, and subsequent TCF-4 and OPN mRNA and protein levels were evaluated by Real-Time PCR and Western blot analysis, respectively.Results:Firstly, we found that the higher mRNA expression ofβ-catenin and OPN (p<0.01) in osteoarthritic chondrocytes compared with normal chondrocytes. Then, the mRNA expression and protein expression of OPN were decreased by DKK-1 affection (p<0.01) in osteoarthritic chondrocytes. After blocking TCF-4 expression by siRNA, we observed that the mRNA and protein expression of TCF-4 and OPN were down-regulatied (p<0.05) in osteoarthritic chondrocytes.Conclusion:1. The expression of OPN is down-regulated by the effect of DKK-1 on theβ-catenin in osteoarthritic chondrocytes.2. The expression of OPN is down-regulated by the lower TCF-4 expression via specific siRNA in osteoarthritic chondrocytes.3. The expression of OPN is regulated viaβ-catenin/TCF-4 complex in Wnt/β-catenin signaling pathway in osteoarthritic chondrocytes.