Anti-FGFBP1 polyclonal antibody

Gene candidate and genome-wide association studies have revealed tens of loci of susceptibility for osteoporosis. Some limitations such as sample size, use of confounding variables, and control for multiple testing and for population stratification, however, represent common problems in these studies that make replication in independent cohorts desirable and even necessary. The main objective of the present study is to replicate previous data on three functional polymorphisms in a cohort of Spanish women. To that end, we performed an association study of three functional polymorphisms previously associated with bone phenotypes in the LRP5, TNFRSF11B, and FGFBP1 genes with low bone mineral density (BMD) in a cohort of 721 Spanish women, most of them postmenopausal. We detected a strong significant association, even when correcting for multiple comparisons, for polymorphism rs312009 in the LRP5 gene with low BMD at the lumbar-spine site. These were women with the CC genotype, which showed the worst bone parameters. Moreover, these women had a higher risk of osteoporosis (adjusted odds ratio 2.82, P = 0.001) than women with the TT/TC genotype. This association seems to be caused because the rs312009 single nucleotide polymorphism (SNP) is located at a binding site for the transcription factor RUNX2 at the 5' region of the LRP5 gene, and the T allele seems to be a better transcriber than the C allele. Regarding the other two SNPs, only the rs4876869 SNP in the TNFRSF11B gene showed a suggestive trend for both skeletal sites. These results underscore the significance of the LRP5 gene in bone metabolism and emphasize the significance of the replication of previous results in independent cohorts.

Rac signaling affects numerous downstream targets in vitro; however, few studies have established in vivo levels. We generated mice with a single knockout (KO) of Rac1 (Keratin5(K5)-Cre;Rac1(flox/flox), Rac1-KO) and double KO of Rac1 and Rac3 (K5-Cre;Rac1(flox/flox);Rac3(-/-), Rac1/Rac3-DKO) in keratinocytes. The hairless phenotype in Rac1-KO mice was markedly exacerbated in Rac1/Rac3-DKO mice. Strikingly, Rac1-KO mice exhibited thinner dermal white adipose tissue, which was considerably further reduced in Rac1/Rac3-DKO mice. DNA microarray using primary keratinocytes from Rac1/Rac3-DKO mice exhibited decreased mRNA levels of Bmp2, Bmp5, Fgf20, Fgf21, Fgfbp1, and Pdgfa. Combinational treatment with bone morphogenetic protein (BMP) 2 and fibroblast growth factor (FGF) 21 in culture medium, but not individual purified recombinant proteins, could differentiate 3T3-L1 fibroblasts into adipocytes, as could culture media from primary keratinocytes. Conversely, addition of anti-BMP2 or anti-FGF21 antibodies into the culture medium inhibited fibroblast differentiation. In addition, BMP2 and FGF21 treatment promoted adipocyte differentiation only of rat primary white adipocyte precursors but not rat primary brown adipocyte precursors. Furthermore, BMP2 and FGF21 treatment enhanced adipogenesis of normal human dermal fibroblasts. Notably, brown adipogenesis promoted by FGF21 was inhibited by BMP2. Thus, we propose a complex paracrine pathway from keratinocytes to intradermal pre-adipocytes, which functions as a Rac-dependent modulator of both white and brown adipogenesis.