Secreted Frizzled-Related Protein 4 Is a Negative Regulator of Peak BMD in SAMP6 Mice

• DOI: 10.1359/jbmr.060719
• Publication Date: 2006-09-29T14:58:12Z
• Authors: Rika Nakanishi; Motoyuki Shimizu; Masayuki Mori; Haruhiko Akiyama; Shuzo Okudaira; Bungo Otsuki; Maiko Hashimoto; Keiichi Higuchi; Masanori Hosokawa; Tadao Tsuboyama; Takashi Nakamura
• Keywords: Congenic; Senescence; Locus coeruleus

We segregated a QTL for peak BMD on Chr 13 by generating congenic sublines of the senescence-accelerated mouse SAMP6. Sfrp 4 within this locus was responsible lower SAMP6.Our genome-wide linkage study using SAMP6 and SAMP2 showed significant quantitative trait (QTL) chromosome (Chr) 13. To verify gene that regulates BMD, we generated strain, P6.P2-Pbd2(b), which carried 15-cM interval an osteoporotic background, Pbd2 increased in SAMP6.To narrow down interval, new subline P6.P2-13. studied effect morphological histomorphological features vivo osteoblasts vitro. The levels expression all genes were examined, clarified candidate gene, secreted frizzled-related protein (Sfrp4), vitro.The P6.P2-13, retained 2.4-Mb 11 existed interval. In morphometrical analysis, P6.P2-13 bone area fraction (BA/TA) 6.6% at diaphysial cortex (p < 0.001) trabecular volume (BV/TV) 54.2% distal metaphysis 0.05) femora compared with those formation rate markedly periosteal surface femoral caused higher proliferation Quantitative RT-PCR analysis calvaria tissue approximately 40-fold Sfrp4 than Taken together result recombinant suppressed osteoblasts, hypothesized inhibited through its antagonistic Wnt signaling. TCF/beta-catenin-dependent reporter activity derived from responsiveness ligand, Wnt3A, P6.P2-13.In mice, negatively decreases inhibition