Roberto Güerri

Publications of Roberto Güerri

• COL1A1 haplotypes and hip fracture.

  Authors: Roser Urreizti, Natàlia Garcia-Giralt, José A Riancho, Jesus González-Macías, Sergi Civit, Roberto Güerri, Guy Yoskovitz, Patricia Sarrion, Leonardo Mellivobsky, Adolfo Díez-Pérez, Xavier Nogués, Susana Balcells, Daniel Grinberg

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 12/2011;

  Fragility fractures resulting from low-trauma events such as a fall from standing height are associated with osteoporosis and are very common in older people, especially women. Three SNPs at theFragility fractures resulting from low-trauma events such as a fall from standing height are associated with osteoporosis and are very common in older people, especially women. Three SNPs at the COL1A1 gene (rs1107946, rs11327935, rs1800012) have been widely studied and previously associated with BMD and fracture. A rare haplotype (T-delT-T) of these three SNPs was found to be greatly overrepresented in fractured individuals compared with non-fractured controls, thus becoming a good candidate for predicting increased fracture risk. The aim of our study was to assess the association of this haplotype with fracture risk in a Spanish cohort. We recruited two independent groups of ∼100 patients with hip fracture (a total of 203 individuals) and compared the genotype and haplotype distributions of the three SNPs in the fractured patients with those of 397 control individuals from the BARCOS Spanish cohort. We found no association with risk of fracture at the genotype level for any of the SNPs, and no differences in the SNP frequencies between the two groups. At the haplotype level, we found no association between the T-delT-T haplotype and fracture. However, we observed a small but significant (p = 0.03) association with another rare haplotype, G-insT-T, which was slightly overrepresented in the patient group. © 2011 American Society for Bone and Mineral Research.

• Functional relevance of the BMD-associated polymorphism rs312009: novel involvement of RUNX2 in LRP5 transcriptional regulation.

  Authors: Lídia Agueda, Rafael Velázquez-Cruz, Roser Urreizti, Guy Yoskovitz, Patricia Sarrión, Susana Jurado, Roberto Güerri, Natàlia Garcia-Giralt, Xavier Nogués, Leonardo Mellibovsky, Adolfo Díez-Pérez, Pierre J Marie, Susana Balcells, Daniel Grinberg

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 05/2011; 26(5):1133-44.

  LRP5 is an osteoporosis susceptibility gene. Association analyses reveal that individual single-nucleotide polymorphisms (SNPs) determine variation in bone mineral density (BMD) among individuals asLRP5 is an osteoporosis susceptibility gene. Association analyses reveal that individual single-nucleotide polymorphisms (SNPs) determine variation in bone mineral density (BMD) among individuals as well as fracture risk. In a previous study, we identified a lumbar spine BMD-associated SNP, rs312009, located in the LRP5 5' region. A RUNX2 binding site was identified in this region by gel-shift experiments. Here we test the functionality of this SNP and examine whether RUNX2 is indeed a regulator of LRP5 expression. Gene reporter assays were used to test rs312009 functionality. Bioinformatic predictive tools and gel-shift and gene reporter assays were used to identify and characterize additional RUNX2 binding elements in the 3.3-kb region upstream of LRP5. Allelic differences in the transcriptional activity of rs312009 were observed in two osteoblastic cell lines, the T allele being a better transcriber than the C allele. RUNX2 cotransfection in HeLa cells revealed that the LRP5 5' region responded to RUNX2 in a dose-dependent manner and that the previously identified RUNX2 binding site participated in this response. Also, RUNX2 inhibition by RNAi led to nearly 60% reduction of endogenous LRP5 mRNA in U-2 OS cells. Four other RUNX2 binding sites were identified in the 5' region of LRP5. Luciferase experiments revealed the involvement of each of them in the RUNX2 response. The allelic differences observed point to the involvement of rs312009 as a functional SNP in the observed association. To our knowledge, this is the first time that the direct action of RUNX2 on LRP5 has been described. This adds evidence to previously described links between two important bone-regulating systems: the RUNX2 transcription-factor cascade and the Wnt signaling pathway.

• Microindentation for in vivo measurement of bone tissue mechanical properties in humans.

  Authors: Adolfo Diez-Perez, Roberto Güerri, Xavier Nogues, Enric Cáceres, Maria Jesus Peña, Leonardo Mellibovsky, Connor Randall, Daniel Bridges, James C Weaver, Alexander Proctor, Davis Brimer, Kurt J Koester, Robert O Ritchie, Paul K Hansma

  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 02/2010; 25(8):1877-85.

  Bone tissue mechanical properties are deemed a key component of bone strength, but their assessment requires invasive procedures. Here we validate a new instrument, a reference point indentationBone tissue mechanical properties are deemed a key component of bone strength, but their assessment requires invasive procedures. Here we validate a new instrument, a reference point indentation (RPI) instrument, for measuring these tissue properties in vivo. The RPI instrument performs bone microindentation testing (BMT) by inserting a probe assembly through the skin covering the tibia and, after displacing periosteum, applying 20 indentation cycles at 2 Hz each with a maximum force of 11 N. We assessed 27 women with osteoporosis-related fractures and 8 controls of comparable ages. Measured total indentation distance (46.0 +/- 14 versus 31.7 +/- 3.3 microm, p = .008) and indentation distance increase (18.1 +/- 5.6 versus 12.3 +/- 2.9 microm, p = .008) were significantly greater in fracture patients than in controls. Areas under the receiver operating characteristic (ROC) curve for the two measurements were 93.1% (95% confidence interval [CI] 83.1-100) and 90.3% (95% CI 73.2-100), respectively. Interobserver coefficient of variation ranged from 8.7% to 15.5%, and the procedure was well tolerated. In a separate study of cadaveric human bone samples (n = 5), crack growth toughness and indentation distance increase correlated (r = -0.9036, p = .018), and scanning electron microscope images of cracks induced by indentation and by experimental fractures were similar. We conclude that BMT, by inducing microscopic fractures, directly measures bone mechanical properties at the tissue level. The technique is feasible for use in clinics with good reproducibility. It discriminates precisely between patients with and without fragility fracture and may provide clinicians and researchers with a direct in vivo measurement of bone tissue resistance to fracture.