Publications (6)16.51 Total impact
-
Article: Trabecular bone deterioration at the greater trochanter of mice with unilateral obstructive nephropathy.
[show abstract] [hide abstract]
ABSTRACT: Our previous study showed the early molecular responses of bone in response to obstructive nephropathy in a unilateral ureteral obstruction (UUO) mouse model. Here, we addressed the changes in trabecular bone properties at greater trochanter, the proximal and the distal metaphysis of femur in UUO mice. The male mice were subjected to UUO (n=10) or sham operation (n=10). All mice were killed on day 7 after the surgical operation. The micro-computed tomography (micro-CT) analysis for different femoral trabecular bone sites demonstrated pathological alterations of trabecular bone mass and micro-networks at greater trochanter as shown by decreases in bone mineral density/bone volume (P<0.05) and trabecular number (P<0.05) and increases in trabecular separation (P<0.01) and bone surface/bone volume (P<0.05) in UUO mice. The present study demonstrates that UUO-induced unilateral obstructive nephropathy has markedly detrimental effects on the trabecular trochanter of the femur.Asian Journal of Andrology advance online publication, 6 May 2013; doi:10.1038/aja.2013.34.Asian Journal of Andrology 05/2013; · 1.52 Impact Factor -
Article: Effects of angiotensin II type 1 receptor blocker on bones in mice with type 1 diabetes induced by streptozotocin.
[show abstract] [hide abstract]
ABSTRACT: INTRODUCTION: This study was performed to address the pathological roles of the skeletal renin-angiotensin system (RAS) in type 1 diabetes-induced osteoporosis and the effects of the angiotensin II type 1 receptor blocker losartan on bones in diabetic mice. MATERIALS AND METHODS: Bone histomorphology was detected by H&E staining, Safranin O staining and X-ray radiography. Micro-CT was performed for the analysis of bone parameters. Gene and protein expression were determined by RT-PCR and immunoblotting. RESULTS: Type 1 diabetic mice displayed osteopenia phenotype, and losartan treatment had no osteoprotective effects on diabetic mice as shown by the reduction of bone mineral density and microarchitectural parameters at the proximal metaphysis of the tibia. The mRNA expression of AGT, renin receptor and ACE, and protein expression of renin and AT1R were markedly up-regulated in the bones of vehicle-treated diabetic mice compared to those of non-diabetic mice. The treatment with losartan further significantly increased the expression of AGT, renin, angiotensin II and AT1R, and reduced the expression of AT2R receptor as compared to those of diabetic mice. CONCLUSION: Local bone RAS functionally played a role in the development of type 1 diabetic osteoporosis, and losartan had no bone-sparing function in diabetes mice because of enhance skeletal RAS activity.Journal of Renin-Angiotensin-Aldosterone System 01/2013; · 2.44 Impact Factor -
Article: Early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice.
[show abstract] [hide abstract]
ABSTRACT: SUMMARY AT A GLANCE: In this study, mice developed hypocalcaemia and hyperparathyroidism following ureteric obstruction. The authors describe subsequent changes in the mRNA expression of target genes and microarchitectrural changes in the proximal tibia, likely to be precursors of renal osteodystrophy. They suggest that in addition to established genetic pathways, the renin-angiotensin system may also be involved ABSTRACT: Aim: This study was performed to address the bone injury and the early molecular responses of bone to obstructive nephropathy induced by unilateral ureteral obstruction in mice. Methods: The male mice were subjected to unilateral ureteral obstruction (UUO, n= 10) or sham operation (n= 10). All mice were killed on day 7 after the surgical operation. H&E and TRAP staining were performed on paraffin-embedded bone sections. Expression of genes and proteins was analyzed by RT-PCR, and western blotting and immunohistochemistry staining, respectively. Results: The serum calcium level was significantly reduced in UUO mice compared to that of Sham mice. The proximal tibia of UUO mice exhibited the increased expansion of chondrocytes zone, the reduction of osteoid content, and the increased separation and disconnection of woven bones. RT-PCR results showed the down-regulation of Cbfa1 and Col mRNA expression and the up-regulation of Tgf-β, CtsK, CaII, Opg and Rankl mRNA expression in tibia of UUO mice compared to those of Sham mice. The ratio of Opg and Rankl was unchanged between Sham and UUO group. Local protein expression of angiotensin II and its type 2 receptor was dramatically up-regulated in tibia of UUO mice. Conclusion: Together, it is concluded that the obstructive nephropathy has defective effects on bone, and the underlying mechanisms are the reduction of bone formation and the increase of bone resorption, which is mediated, at least partially through local angiotensin II signaling. © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.Nephrology 09/2012; · 1.31 Impact Factor -
Article: Involvement of the skeletal Renin-Angiotensin system in age-related osteoporosis of ageing mice.
[show abstract] [hide abstract]
ABSTRACT: The local tissue-specific renin-angiotensin system (RAS) was identified. The aim of this study was to investigate the role of local bone RAS in the osteoporosis of aging mice. Twelve-month-old and two-month-old male mice were respectively assigned to the ageing and young groups. The tibias and femurs were collected for an analysis of histomorphology, bone mass, and gene and protein expression. H&E staining and micro-CT measurement showed a loss of the trabecular bone network and decrease of bone mineral density in the proximal tibial metaphysis of the aged mice. The PCR results indicated the significant up-regulation of renin and angiotensinogen (AGT) mRNA expression in both the tibia and femur of the ageing mice. Western blotting data showed that the tibial angiotensin II protein expression was significantly increased in the ageing group. The enhancement of renin and AGT expression in the bone tissue resulted in the increased production of angiotensin II which plays an important role in the pathology of age-related osteoporosis.Bioscience Biotechnology and Biochemistry 07/2012; 76(7):1367-71. · 1.28 Impact Factor -
Article: Genome-wide association study of copy number variation identified gremlin1 as a candidate gene for lean body mass.
[show abstract] [hide abstract]
ABSTRACT: Lean body mass (LBM) is a heritable trait predicting a series of health problems, such as osteoporotic fracture and sarcopenia. We aim to identify sequence variants associated with LBM by a genome-wide association study (GWAS) of copy number variants (CNVs). We genotyped genome-wide CNVs of 1627 individuals of the Chinese population with Affymetrix SNP6.0 genotyping platform, which comprised of 9 40 000 copy number probes. We then performed a GWAS of CNVs with lean mass at seven sites: left and right arms, left and right legs, total of limb, trunk and whole body. We identified a CNV that is associated with LBM variation at the genome-wide significance level (CNV2073, Bonferroni corrected P-value 0.002 at right arm). CNV2073 locates at chromosome 15q13.3, which has been implicated as a candidate region for LBM by our previous linkage studies. The nearest gene, gremlin1, has a key role in the regulation of skeletal muscle formation and repair. Our results suggest that the gremlin1 gene is a potentially important gene for LBM variation. Our findings also show the utility and efficacy of CNV as genetic markers in association studies.Journal of Human Genetics 11/2011; 57(1):33-7. · 2.57 Impact Factor -
Article: Peripheral blood monocyte-expressed ANXA2 gene is involved in pathogenesis of osteoporosis in humans.
[show abstract] [hide abstract]
ABSTRACT: Low bone mineral density (BMD) is a risk factor of osteoporosis and has strong genetic determination. Genes influencing BMD and fundamental mechanisms leading to osteoporosis have yet to be fully determined. Peripheral blood monocytes (PBM) are potential osteoclast precursors, which could access to bone resorption surfaces and differentiate into osteoclasts to resorb bone. Herein, we attempted to identify osteoporosis susceptibility gene(s) and characterize their function(s), through an initial proteomics discovery study on PBM in vivo, and multiscale validation studies in vivo and in vitro. Utilizing the quantitative proteomics methodology LC-nano-ESI-MS(E), we discovered that a novel protein, i.e. ANXA2, was up-regulated twofold in PBM in vivo in Caucasians with extremely low BMD (cases) versus those with extremely high BMD (controls) (n = 28, p < 0.05). ANXA2 gene up-regulation in low BMD subjects was replicated at the mRNA level in PBM in vivo in a second and independent case-control sample (n = 80, p < 0.05). At the DNA level, we found that SNPs in the ANXA2 gene were associated with BMD variation in a 3(rd) and independent case-control sample (n = 44, p < 0.05), as well as in a random population sample (n = 997, p < 0.05). The above integrative evidence strongly supports the concept that ANXA2 is involved in the pathogenesis of osteoporosis in humans. Through a follow-up cellular functional study, we found that ANXA2 protein significantly promoted monocyte migration across an endothelial barrier in vitro (p < 0.001). Thus, elevated ANXA2 protein expression level, as detected in low BMD subjects, probably stimulates more PBM migration through the blood vessel walls to bone resorption surfaces in vivo, where they differentiate into higher number of osteoclasts and resorb bone at higher rates, thereby decreasing BMD. In conclusion, this study identified a novel osteoporosis susceptibility gene ANXA2, and suggested a novel pathophysiological mechanism, mediated by ANXA2, for osteoporosis in humans.Molecular & Cellular Proteomics 08/2011; 10(11):M111.011700. · 7.40 Impact Factor
Top co-authors
Top Journals
Institutions
-
2011–2013
-
University of Shanghai for Science and Technology
Shanghai, Shanghai Shi, China
-
-
2011–2012
-
Tulane University
- Center for Bioinformatics and Genomics
New Orleans, LA, USA
-
