Lrp5-knockout inhibits aging-induced and destabilization of the medial meniscus–induced osteoarthritic cartilage destruction. (A) Spontaneous osteoarthritis (OA) in Lrp5-knockout (Lrp5-KO; Lrp5-/-) mice was examined at 12 months of age and compared with that in wild-type (WT) mice (n = 10 independent experimental animals). (B) Sham operation in the left knee joint and destabilization of the medial meniscus (DMM) surgery in the right knee joint were performed in WT and Lrp5-/- mice (n = 20). Cartilage destruction was examined by Safranin O and hematoxylin staining of cartilage sections and measured by Mankin score. Values are expressed as means ± SEM (*P < 0.005). Scale bar: 50 μm. The presented immunostaining images of LRP5 in the knee articular cartilage are representative of at least seven independent tissue samples. (C) through (E) Chondrocytes obtained from WT and Lrp5-/- mice were treated with the indicated concentrations (in nanograms per milliliter) of recombinant interleukin 1β (IL-1β) (C), Wnt3a (D) or Wnt7a (E), and the mRNA expression levels of Lrp5, Col2a1, Mmp3 and Mmp13 were assessed by RT-PCR. C: control, BSA: bovine serum albumin.