Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of beta-tricalcium phosphate (beta-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats. Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous beta-TCP loaded with BMP-2 gene- or beta-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or beta-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the beta-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the beta-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the beta-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the beta-gal group. The maximum compressive strength and Young's modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the beta-gal group. Our findings indicate that porous beta-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function.
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PMID:Treatment of osteonecrosis of the femoral head with hBMP-2-gene-modified tissue-engineered bone in goats. 1725 31

Endothelial cells subjected to glycated collagen I develop premature senescence within 3-5 days, as revealed by increased senescence-associated beta-galactosidase activity, decreased proliferation, and an increase in cell size. Here, we analyzed the time course and possible mechanisms of this process. Lysosomal integrity studies revealed a rapid collapse of pH gradient and lysosomal permeabilization, detectable after 30 min, and preceded by the increased production of reactive oxygen species. Measurement of mitochondrial membrane potential after application of glycated collagen demonstrated that depolarization was delayed by 4 h compared with changes in lysosomal pH and permeability. Based on the above findings of lysosomal permeabilization, we hypothesized that the reduced activity of senescence-associated beta-galactosidase could be responsible for the cellular accumulation of gangliosides, previously shown to induce cell senescence. After 5 days of exposure to glycated collagen, there was an increase in the levels of gangliosides GM3, GD1b, and GT1b, coincident with development of cell senescence. Treatment of endothelial cells with d-threo-EtDOP4, an inhibitor of glucosylceramide synthase, inhibited apoptosis, but not the development of senescence. In conclusion, collagen I modified by advanced glycation initially induces apoptosis of human umbilical vein endothelial cells. This process is initiated by the collapse of lysosomal pH and an increase in lysosomal permeability, with the subsequent mitochondrial depolarization and accumulation of gangliosides. Blockade of ganglioside synthesis suppresses apoptosis, but not senescence, which develops after 3 days of exposure to glycated collagen. These data imply a critical role for lysosomal permeabilization in triggering apoptosis of endothelial cells exposed to the diabetic milieu.
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PMID:Mapping mechanisms and charting the time course of premature cell senescence and apoptosis: lysosomal dysfunction and ganglioside accumulation in endothelial cells. 1792 15


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