Decreased Indian hedgehog signaling inhibits Ihh downstream targets in osteoarthritis cartilage. (A) Indian hedgehog (Ihh) deletion leads to downregulation of Ihh downstream targets in osteoarthritis (OA) cartilage 2 months after partial medial meniscectomy. (a) Laser-captured microdissection was used to analyze gene expression in articular cartilage. Articular cartilage (highlighted in red) before and after microdissection is shown. (b) Results of real-time PCR are shown. The expression of Ihh, Gli1, Gli2, matrix metalloprotease (MMP-13), type X collagen (Col X) and Runx2 was significantly decreased, and the expression of aggrecan and type II collagen (Col II) was increased, respectively, in the Ihh-deleted mice (tamoxifen (TM)) (n = 6) compared to the control animals (no TM) (n = 8). Data are means ± SD. *P < 0.00001, #P < 0.0005, +P < 0.001, ^P < 0.05. (B) Cyclopamine decreased expression of Gli1, MMP-13 and type X collagen in human OA cartilage. Relative mRNA levels in human cartilage organ cultures 48 hours after treatment with cyclopamine (n = 8) and dimethyl sulfoxide (DMSO) controls (n = 8) are shown. Data are means ± SD (n = 8). *#^P < 0.0001.