Min Zhu

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (3)19.39 Total impact

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    ABSTRACT: To assess the effect of hypoparathyroidsm on osteogenesis and bone turnover in vivo, bone marrow ablations (BMX) were performed in tibiae of 8-week-old wild-type and PTH null (PTH(-/-) ) mice and newly formed bone tissue was analyzed from 5 days to 3 weeks after BMX. At 1 week after BMX, trabecular bone volume, osteoblast numbers, alkaline phosphatase-positive areas, type I collagen-positive areas, PTH receptor-positive areas, calcium sensing receptor-positive areas and expression of bone formation-related genes, were all decreased significantly in the diaphyseal regions of bones of PTH(-/-) mice compared to wild-type mice. In contrast, by 2 weeks after BMX all parameters related to osteoblastic bone accrual were increased significantly in PTH(-/-) mice. At 5 days after BMX, active TRAP positive osteoclasts had appeared in wild-type mice but were undetectable in PTH(-/-) mice, Both the ratio of mRNA levels of RANKL/OPG and TRAP positive osteoclast surface were still reduced in PTH(-/-) mice at 1 week but increased by 2 weeks after BMX. The expression levels of PTHrP at both mRNA and protein levels were up-regulated significantly at 1 week and more dramatically at 2 weeks after BMX in PTH(-/-) mice. To determine whether the increased newly formed bones in PTH(-/-) mice at 2 weeks after BMX resulted from the compensatory action of PTHrP, PTH(-/-) PTHrP(+/-) mice were generated and newly formed bone tissue was compared in these mice with PTH(-/-) and wild-type mice at 2 weeks after BMX. All parameters related to osteoblastic bone formation and osteoclastic bone resorption were reduced significantly in PTH(-/-) PTHrP(+/-) mice compared to PTH(-/-) mice. These results demonstrate that PTH deficiency itself impairs osteogenesis, osteoclastogenesis and osteoclastic bone resorption, whereas subsequent up-regulation of PTHrP in osteogenic cells compensates by increasing bone accrual.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 05/2013; 28(9). · 6.04 Impact Factor
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    ABSTRACT: Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining endogenous antioxidant defenses in the brain, and its absence subsequently causes premature brain degeneration.
    PLoS ONE 07/2012; 7(2):e32015. · 3.53 Impact Factor
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    ABSTRACT: Parathyroid hormone (PTH) plays a central role in the regulation of serum calcium and phosphorus homeostasis, while parathyroid hormone-related protein (PTHrP) has important developmental roles. Both peptides signal through the same G protein-coupled receptor, the PTH/PTHrP or PTH type 1 receptor (PTH1R). PTHrP, normally a secreted protein, also contains a nuclear localization signal (NLS) that in vitro imparts functionality to the protein at the level of the nucleus. We investigated this functionality in vivo by introducing a premature termination codon in Pthrp in ES cells and generating mice that express PTHrP (1-84), a truncated form of the protein that is missing the NLS and the C-terminal region of the protein but can still signal through its cell surface receptor. Mice homozygous for the knock-in mutation (Pthrp KI) displayed retarded growth, early senescence, and malnutrition leading postnatally to their rapid demise. Decreased cellular proliferative capacity and increased apoptosis in multiple tissues including bone and bone marrow cells were associated with altered expression and subcellular distribution of the senescence-associated tumor suppressor proteins p16(INK4a) and p21 and the oncogenes Cyclin D, pRb, and Bmi-1. These findings provide in vivo experimental proof that substantiates the biologic relevance of the NLS and C-terminal portion of PTHrP, a polypeptide ligand that signals mainly via a cell surface G protein-coupled receptor.
    Proceedings of the National Academy of Sciences 01/2009; 105(51):20309-14. · 9.81 Impact Factor