Severe joint destruction and osteoporosis in KRN/G7 mice. (A) Radiographs of femurs of 6-week-old G7 and KRNxG7 mice. (Right panels) Higher magnification images of boxed areas in the left panels. Yellow arrow and dashed circle in lower right panel denote destroyed articular surface and secondary ossification center, respectively. Red arrow points to trabecular bone region. Green arrow indicates microfractures. (B) Representative 3-dimensional reconstruction of the femur by μCT. (C) The percentage of trabecular bone volume/tissue volume (BV/TV) determined by μCT. (D) Trabecular separation determined by μCT (Tb. space). (E) Dual-energy X-ray absorptiometry determined bone mineral density (BMD). Data are presented as mean ± SD; n = 5 in each group of mice. (F) Histomorphometric determination of BV/TV. Trabecular bone volume normalized to total marrow space (BV/TV). (G) TRAP (red reaction product) stained histologic sections of G7 and KRNxG7 tibia. Data are expressed as percentage trabecular bone surface covered by osteoclasts; n = 5. (H) Global osteoclast number, in vivo, was quantified by serum TRAP5b enzyme-linked immunosorbent assay. (I) Oscar, integrin β3, and cathepsin K expression was analyzed by quantitative polymerase chain reaction (PCR) with RNA from G7 and KRNxG7 BM. Shown is the mean expression ± SD for each gene normalized to GAPDH; n = 3. (J) SDF1 and TNF-α expression was analyzed by quantitative reverse-transcribed (RT)–PCR with RNA from G7 and KRNxG7 BM. Shown is the mean expression ± SD for each gene normalized to GAPDH; n = 3. *P < .05. **P < .01. ***P < .001.