Osteoporosis as a systemic chronic skeletal disease is characterized by low bone mineral density and increased risk to osteoporotic fractures.Osteoporosis is prevalent in the middle-aged and elderly population,especia...Osteoporosis as a systemic chronic skeletal disease is characterized by low bone mineral density and increased risk to osteoporotic fractures.Osteoporosis is prevalent in the middle-aged and elderly population,especially in the postmenopausal women.With population aging,osteoporosis has become a world-wide serious public health problem.Early recognition of the high-risk population followed by timely and efficient intervention and/or treatment is important for preventing osteoporotic fractures.In light of the high heritability and complex pathogenesis of osteoporosis,comprehensive consideration of vital biological/biochemical factors is necessary for accurate risk evaluation of fractures.For this purpose,we review recent research progress on molecules which can be applied to assess risk for osteoporotic fractures.Future integrative analyses and systematic evaluation of these molecules may facilitate developing novel methodologies and/or test strategies,i.e.,biochips,for early recognition of osteoporosis,hence contributing to preventing osteoporotic fractures.展开更多
To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic an...To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.展开更多
Activation of TLR signaling is a first line of the host defense system in the elimination of invading pathogens.1 Insulin-like growth factor binding protein, acid-labile subunit (IGFALS) is a leucine-rich glycoprotein...Activation of TLR signaling is a first line of the host defense system in the elimination of invading pathogens.1 Insulin-like growth factor binding protein, acid-labile subunit (IGFALS) is a leucine-rich glycoprotein. By prolonging the half-life of IGF-I in the vascular system,2 IGFALS regulates the bioavailability of IGF, which is crucial for normal growth and development and metabolic regulation.3,4 However, the role of IGFALS in antiviral innate immune responses has not been established. In this study, we found that IGFALS is virus inducible, while it in turn inhibits viral replication. Mechanistically, IGFALS directly associates with IRAK1 and TRAF6, facilitating IRAK1/TRAF6 complex formation and enhancing K63-linked polyubiquitination of both proteins for full activation, thereby facilitating antiviral signaling.展开更多
基金the Startup Fund from Soochow University(Q413900712)the Project of the Priority Academic Program Development of Jiangsu Higher Education Institution.
文摘Osteoporosis as a systemic chronic skeletal disease is characterized by low bone mineral density and increased risk to osteoporotic fractures.Osteoporosis is prevalent in the middle-aged and elderly population,especially in the postmenopausal women.With population aging,osteoporosis has become a world-wide serious public health problem.Early recognition of the high-risk population followed by timely and efficient intervention and/or treatment is important for preventing osteoporotic fractures.In light of the high heritability and complex pathogenesis of osteoporosis,comprehensive consideration of vital biological/biochemical factors is necessary for accurate risk evaluation of fractures.For this purpose,we review recent research progress on molecules which can be applied to assess risk for osteoporotic fractures.Future integrative analyses and systematic evaluation of these molecules may facilitate developing novel methodologies and/or test strategies,i.e.,biochips,for early recognition of osteoporosis,hence contributing to preventing osteoporotic fractures.
基金supported by grants from NIH in USA (No. K01 AR02170-01, R01 AR45349-01, R01 GM60402-01 A1, R01 AG026564-01A2, and R21 AG027110-01A1)the Natural Science Foundation o China (NSFC) (No. 30600364)The genotyping experiment was performed by Marshfield Center for Medical Genetics and supported by NHLB Mammalian Genotyping Service (Contract No. HV48141)
文摘To quantify the genetic correlations between total body fat mass （TBFM） and femoral neck geometric parameters （FNGPs） and, if pos- sible, to detect the specific genomic regions shared by them, bivariate genetic analysis and bivariate whole-genome linkage scan were carried out in a large Caucasian population. All the phenotypes studied were significantly controlled by genetic factors （P 〈 0.001） with the heritabilities ranging from 0.45 to 0.68. Significantly genetic correlations were found between TBFM and CSA （cross-section area）, W （sub-periosteal diameter）, Z （section modulus） and CT （cortical thickness） except between TBFM and BR （buckling ratio）. The peak bivariate LOD scores were 3.23 （20q12）, 2.47 （20p11）, 3.19 （6q27）, 1.68 （20p12）, and 2.47 （7q11） for the five pairs of TBFM and BR, CSA, CT, W, and Z in the entire sample, respectively. Gender-specific bivariate linkage evidences were also found for the five pairs. 6p25 had complete pleiotropic effects on the variations of TBFM ＆ Z in the female sub-population, and 6q27 and 17q11 had coincident link- ages for TBFM ＆ CSA and TBFM ＆ Z in the entire population. We identified moderate genetic correlations and several shared genomic regions between TBFM and FNGPs in a large Caucasian population.
基金supported by a research grant from the National Natural Science Foundation of China(81971494).
文摘Activation of TLR signaling is a first line of the host defense system in the elimination of invading pathogens.1 Insulin-like growth factor binding protein, acid-labile subunit (IGFALS) is a leucine-rich glycoprotein. By prolonging the half-life of IGF-I in the vascular system,2 IGFALS regulates the bioavailability of IGF, which is crucial for normal growth and development and metabolic regulation.3,4 However, the role of IGFALS in antiviral innate immune responses has not been established. In this study, we found that IGFALS is virus inducible, while it in turn inhibits viral replication. Mechanistically, IGFALS directly associates with IRAK1 and TRAF6, facilitating IRAK1/TRAF6 complex formation and enhancing K63-linked polyubiquitination of both proteins for full activation, thereby facilitating antiviral signaling.
