Figure 4 | Scientific Reports

Figure 4

From: Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis

Figure 4

Mianserin ameliorates OA progression and reduces β-catenin expression in a rat model of OA. (A) Destabilization of medial meniscus (DMM) surgery was performed on the right knees of 6 Wistar/ST rats. Sham surgery was performed on the contralateral left knees by incising the skin and joint capsules. Fifty microliters PBS (n = 3) or 50 μM mianserin dissolved in 50 μl PBS (n = 3) was injected intraarticularly into both knees once weekly for 8 weeks after surgery. Representative histological sections of the medial compartments in the knee joints stained with Safranin-O and Fast-green are shown. (B) OA severity in the medial compartment of the knee joint was quantified by modified Mankin score at 8 weeks after the surgery. The sum of femoral and tibial scores is shown by mean and SD. *P < 0.05 by one-way ANOVA followed by Tukey’s post-hoc test. There was no statistical significance between PBS and mianserin in the DMM group (P = 0.079). (C) Left panels show magnifications of the boxed areas in A. Right panels show immunostaining with anti-β-catenin antibody in serial sections of the left panels. (D) Magnifications of the boxed areas in (C). Articular chondrocytes are stained with anti-β-catenin antibody and DAPI. (E,F) Blinded morphometry of β-catenin signals of the chondrocytes at the medial compartments with MetaMorph. (E) Signal intensities for β-catenin in the total cellular area and the DAPI-positive nuclear area are normalized to the number of cells and also to that in total cellular area in PBS-treated cartilage. **P < 0.01 by one-way ANOVA followed by Tukey’s post-hoc test. Mean and SD are indicated (n = 3 knees in each group). (F) The number of β-catenin-positive cells is divided by the number of DAPI signals to calculate the ratio of nuclear β-catenin-positive cells. The number of β-catenin-positive cells is divided by the number of DAPI signals to calculate the ratio of nuclear β-catenin-positive cells. *P < 0.05 by one-way ANOVA followed by Tukey’s post-hoc test. Scale bar = 200 μm (A), 100 µm (C), and 25 µm (D). (G) Model of Rspo2-mediated OA development, and the effect of mianserin.

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