Activation of bone morphogenetic protein signaling in the mouse knee during collagen-induced arthritis. Immunohistochemistry for P-SMAD1/5 in the initial phase (a, b), with increasing severity (c-f), and in the destructive phase of collagen-induced arthritis (g, h) and IgG control (j) is shown. Scoring was done on sections stained with hematoxylin and eosin (a, c, e, g, i). Boxes indicate areas that are magnified in P-SMAD1/5 stainings (b, d, f, h). Arrows indicate P-SMAD1/5-positive cells, and arrowheads indicate P-SMAD1/5-positive blood vessels. Bars = 200 μm (a, c, e, g, i), 50 μm (d, f, h), and 25 μm (b). P-SMAD, phosphorylated Smad family members; SMAD, Smad family members.