Impaired osteoclast differentiation/activation within the joints of fXIIIA-deficient mice. (A) Representative images of knee joint sections harvested from CIA-challenged fXIIIA^+/+ and fXIIIA^−/− mice stained for TRAP. Note numerous TRAP⁺, multinucleated osteoclasts (arrows) within erosive lesions of fXIIIA^+/+ knee joints, but largely absent in sections from fXIII^−/− mice. The * indicates area of intact bone. Quantitative RT-PCR analysis mRNA for (B) TRAP gene expression, (C) NFATc1, (D) RANKL gene expression, and (E) OPG gene expression within hind paw joints harvested from unchallenged and CIA-challenged fXIIIA^+/+ and fXIIIA^−/− mice. Data are expressed as average fold change relative to unchallenged fXIIIA^+/+ group. (F) Ratio of RANKL and OPG relative expression. (G) Quantitative RT-PCR analysis of local mRNA levels of TRAP, RANKL, OPG, and the ratio of RANKL/OPG in the hind paws of unchallenged Fib⁺ and Fib− mice (n = 6 per genotype). All data are expressed as mean ± standard error of the mean. Data were analyzed by 2-way analysis of variance followed by Student-Newman-Keuls posthoc test in which *P < .05; **P < .01. NS = not significant (B-G). Scale bar represents 200 μm (top panels) and 10 μm (bottom panels) (A).