LRP5 is upregulated in human and mouse experimental osteoarthritic cartilage. (A) Undamaged (Normal/Nor) and damaged (osteoarthritis (OA)) human OA cartilage were examined with Alcian blue staining and immunostaining for LRP5. Six patients were independently assessed, and a typical result is presented. The mRNA levels of Lrp5 and Lrp6 in undamaged and damaged OA cartilage were examined by RT-PCR and measured by quantitative RT-PCR (qRT-PCR). (B) through (D) Safranin O staining and immunostaining for LRP5 were performed on cartilage samples from STR/ort (STR) OA mice and control CBA/CaCrl (CBA) mice (n = 8) (B); C57BL/6 mice after intra-articular injection of collagenase (Coll) or control phosphate-buffered saline (n = 6) (C); and C57BL/6 mice subjected to sham or destabilization of the medial meniscus (DMM) surgery (n = 10) (D). Lrp5 and Lrp6 mRNA levels were examined by RT-PCR and quantified by qRT-PCR (B) through (D). Cartilage destruction was evaluated by International Cartilage Repair Society (ICRS) grade for human cartilage samples (A) and by Mankin score for mouse cartilage (B) through (D). Values are presented as means ± SEM (*P < 0.01, **P < 0.001; n > 7). Scale bar: 50 μm.