The insulin-like growth factor-I gene and osteoporosis: A critical appraisal

Niu, Tianhua; Rosen, Clifford J.

doi:10.1016/j.gene.2005.07.016

Cited by 140 publications

(95 citation statements)

References 233 publications

(261 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pleiotropic loci affecting many traits and having high LPRs may include genes with strong impacts on whole skeletal development, such as those that encode certain hormones. For example, we would expect to detect a QTL at insulin-like growth factor 1 (Igf-1), given its known effects on skeletal growth (Niu and Rosen 2005), and indeed it is located within the confidence interval of pleiotropic locus Skl10.03, which affects 14 traits and has an LPR of 9.00.…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic Patterns of Quantitative Trait Loci for 70 Murine Skeletal Traits

et al. 2008

View full text Add to dashboard Cite

Quantitative trait locus (QTL) studies of a skeletal trait or a few related skeletal components are becoming commonplace, but as yet there has been no investigation of pleiotropic patterns throughout the skeleton. We present a comprehensive survey of pleiotropic patterns affecting mouse skeletal morphology in an intercross of LG/J and SM/J inbred strains (N ¼ 1040), using QTL analysis on 70 skeletal traits. We identify 798 singletrait QTL, coalescing to 105 loci that affect on average 7-8 traits each. The number of traits affected per locus ranges from only 1 trait to 30 traits. Individual traits average 11 QTL each, ranging from 4 to 20. Skeletal traits are affected by many, small-effect loci. Significant additive genotypic values average 0.23 standard deviation (SD) units. Fifty percent of loci show codominance with heterozygotes having intermediate phenotypic values. When dominance does occur, the LG/J allele tends to be dominant to the SM/J allele (30% vs. 8%). Over-and underdominance are relatively rare (12%). Approximately one-fifth of QTL are sex specific, including many for pelvic traits. Evaluating the pleiotropic relationships of skeletal traits is important in understanding the role of genetic variation in the growth and development of the skeleton.

show abstract

Section: Discussionmentioning

confidence: 99%

Pleiotropic Patterns of Quantitative Trait Loci for 70 Murine Skeletal Traits

et al. 2008

View full text Add to dashboard Cite

show abstract

“…However, expression of the downstream transcription factor osterix, also required for osteoblast differentiation [56,57] was similar in both e-CSC transplanted oim and nontransplanted controls (3.7 · 10 -2 -0.5 · 10 -2 $2 -DCt vs. 3.3 · 10 -2 -0.7 · 10 -2 $2 -DCt respectively). In contrast Igf1, which regulates both osteoblasts [58] and osteoclastogenesis via induction of RANK-L synthesis [59,60] and stimulates linear growth [61] was upregulated in transplanted mice (0.43 -0.05$2 -DCt vs. 0.21 -0.02$2 -DCt for oim controls, P < 0.05). Expression of endogenous ossification genes correlated linearly with their co-activators and trans-activation targets as expected when mice were analyzed on an individual basis.…”

Section: Upregulation Of Genes Activated During Intramembraneous Ossimentioning

confidence: 94%

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

Jones

Moschidou

Abdulrazzak

et al. 2014

Stem Cells and Development

View full text Add to dashboard Cite

Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.

show abstract

“…Previous studies have reported that the expression of IGF-1 polymorphisms might affect the development of osteoporosis; however, the results have been inconsistent (Kim et al, 2002;Rivadeneira et al, 2003;Jiang et al, 2005;Niu and Rosen, 2005;Yun-Kai et al, 2014). In our study, we suggested that the IGF-1 rs2288377 and rs972936 gene polymorphisms were not associated with osteoporosis risk in Chinese postmenopausal women, and that the CT+TT genotype of rs35767 and the AG+GG genotype of rs972936 were significantly associated with lower BMD levels in the femoral necks of these patients.…”

Section: Discussionmentioning

confidence: 97%

Association of the IGF-1 rs35767 and rs972936 polymorphisms with the risk of osteoporosis in a Chinese postmenopausal female population

Wei

L²,

Guo³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The aim of our study was to conduct a case-control study in a Chinese postmenopausal population to evaluate the roles of the IGF-1 rs35767 and rs972936 polymorphisms on bone mineral density (BMD) levels and osteoporosis risk. A total of 272 consecutive postmenopausal women with a primary diagnosis of osteoporosis and 272 controls were enrolled in the study between 2012 and 2014. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype the rs35767 and rs972936 IGF-1 polymorphisms. By comparing the demographic characteristics between patients and controls, patients with osteoporosis were found to be more likely to have a habit of alcohol drinking (P = 0.023). Furthermore, the BMD levels of the L 1 -L 4 vertebrae, femoral necks, total hips, and trochanters in patients with osteoporosis were significantly lower than those in controls. By conditional regression analysis, we found that the IGF-1 rs2288377 and rs972936 gene polymorphisms (2015) were not associated with the risk of osteoporosis (P < 0.05). However, the CT+TT genotype of rs35767 and the AG+GG genotype of rs972936 were significantly associated with lower BMD levels in the femoral neck. Overall, our study suggests that IGF-1 rs2288377 and rs972936 gene polymorphisms do not influence the risk osteoporosis.

show abstract

The insulin-like growth factor-I gene and osteoporosis: A critical appraisal

Cited by 140 publications

References 233 publications

Pleiotropic Patterns of Quantitative Trait Loci for 70 Murine Skeletal Traits

Pleiotropic Patterns of Quantitative Trait Loci for 70 Murine Skeletal Traits

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

Association of the IGF-1 rs35767 and rs972936 polymorphisms with the risk of osteoporosis in a Chinese postmenopausal female population

Contact Info

Product

Resources

About