Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of stem cells is promising for future cell-based therapy such as tissue regeneration and engineering. Although Embryonic Stem Cells (ESCs) are theoretically highly beneficial, there are some potential limitations of cell regulations and ethical consideration. Mesenchymal Stem Cells (MSCs) isolated from bone marrow stroma have been shown to possess adipogenic, osteogenic, chondrogenic, myogenic and neurogenic potential in vitro. However, bone marrow procurement is severely painful for donors and often requires general anesthesia. Moreover, only small numbers of cells can be harvested. We previously hypothesized that human adipose tissue obtained from liposuction procedures also contains the same cell population as MSCs, because adipose tissue is mesenchymal in origin, like bone marrow stroma. Subsequent studies revealed that: (1) cell population (which we termed Processed Lipoaspirate [PLA] cells), observed by indirect immunofluorescence study of adipose tissue, consist of cells of mesenchymal origin that have little contamination with endothelial cells, smooth muscle cells and pericytes; (2) these PLA cells exhibit low levels of cell senescence even after multiple passage, as demonstrated by beta-galactosidase staining assay; and (3) PLA cells can differentiate into adipogenic, osteogenic, chondrogenic and myogenic cells in vitro in lineage-specific culture media. These findings suggest that human PLA might have a mesodermal stem cell population. Since human adipose tissue is plentiful, easily harvested in large quantity under local anesthesia with little patient discomfort, it may be an alternative stem cell source for mesenchymal tissue regeneration and engineering. This review highlights our previous research work on PLA cells and future clinical perspectives, particularly in the field of plastic and reconstructive surgery.
...
PMID:Mesengenic potential and future clinical perspective of human processed lipoaspirate cells. 1292 9

The osteogenic cell type of human periodontal ligament fibroblasts (PDLF) undergoes senescence at finite population doubling numbers unrelated to donor ages. This study investigated telomere lengths of osteogenic PDLF from differently aged donors and alterations of the osteoblast-like properties in the aged PDLF with short telomeres. Telomere lengths of osteogenic PDLF were biased towards long or short among all 15- to 51-year-old individuals, and did not show a normal distribution by Pearson's test or a correlation to donor age by simple regression analysis. In osteogenic PDLF, senescence-associated beta-galactosidase was expressed in 78.5% of cells in the clones with short telomeres (mean 3.02 kbp), and in 9.4% of cells in the clones with long telomeres (mean 13.06 kbp). These results suggest that human periodontium comprises aged osteogenic PDLF without correlation to age. Osteogenic PDLF with long telomeres strongly expressed alkaline phosphatase (ALPase) activity whereas cells with short telomeres expressed ALPase activity to a weaker extent. Total activity of ALPase in the clones of osteogenic PDLF with long telomeres was significantly higher than that in the clones with short telomeres. The produced amounts of both osteopontin and osteocalcin in the clones of osteogenic PDLF with long telomeres were slightly but statistically significantly smaller than those in the clones with short telomeres. These findings suggest that aged osteogenic PDLF reduce the expression of ALPase activity but that there is not a critical alteration in bone-associated protein production. Aged osteogenic PDLF may impair the ability to induce ALPase-dependent calcification.
...
PMID:Reduction of alkaline phosphatase activity in aged human osteogenic periodontal ligament fibroblasts exhibiting short telomeres. 1467 42

Age-related decrease in bone formation is well described. However, the cellular causes are not known. Thus, we have established cultures of bone marrow stromal cells (MSC) from young (aged 18-29 years, n = 6) and old (aged 68-81 years, n = 5) donors. MSC were serially passaged until reaching maximal life span. Cell growth, markers of cellular senescence, and osteogenic and adipogenic potential were determined in early-passage and late-passage cells established from young and old donors. MSC from old donors exhibited a decreased maximal life span compared with cells from young donors (24 +/- 11 population doublings [PD] vs 41 +/- 10 PD, P < 0.05) and mean PD rate was lower in old donor cells (0.05 +/- 0.02 PD/day) compared with young donor cells (0.09 +/- 0.02 PD/day) (P < 0.05). No differences were detected in number of senescence-associated beta-galactosidase positive (SA beta-gal+) cells and mean telomere length in early-passage cells obtained from young and old donors. However, MSC from old donors exhibited accelerated senescence evidenced by increased number of SA beta-gal+ cells per PD as compared with young (4% per PD vs 0.4% per PD, respectively). MSC from young and old donors were able to form similar amounts of mineralized matrix in vitro and of normal lamellar bone in vivo. In adipogenic medium similar numbers of adipocytes formed in cultures of young and old donors. In conclusion, aging is associated with decreased proliferative capacity of osteoprogenitor cells, suggesting that decreased osteoblastic cell number, and not function, leads to age-related decrease in bone formation.
...
PMID:Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. 1467 51

Structural bone allografts often fracture due to their lack of osteogenic and remodeling potential. To overcome these limitations, we utilized allografts coated with recombinant adeno-associated virus (rAAV) that mediate in vivo gene transfer. Using beta-galactosidase as a reporter gene, we show that 4-mm murine femoral allografts coated with rAAV-LacZ are capable of transducing adjacent inflammatory cells and osteoblasts in the fracture callus following transplantation. While this LacZ vector had no effect on allograft healing, bone morphogenetic protein signals delivered via rAAV-caAlk2 coating induced endochondral bone formation directly on the cortical surface of the allograft by day 14. By day 28 there was evidence of remodeling of the new woven bone and massive osteoclastic resorption of the cortical surface of the rAAV-caAlk2-coated allografts only. Micro-CT analysis of rAAV-LacZ- vs rAAV-caAlk2-coated allografts after 42 days of healing demonstrated a significant increase in new bone formation (0.67 +/- 0.21 vs 2.49 +/- 0.40 mm(3); P < 0.005). Furthermore, the 3D micro-CT images of femurs grafted with rAAV-Alk2-coated allografts provided the first evidence that complete bridging of bone around a cortical allograft is possible. These results indicate that cell-free, rAAV-coated allografts have the potential to revitalize in vivo following transplantation.
...
PMID:Biological effects of rAAV-caAlk2 coating on structural allograft healing. 1604 92

Marrow stromal cells (MSCs) have the potential to differentiate into multiple mesenchymal cell types. To harness the power of MSCs for bone regeneration, methods must be developed to direct their differentiation selectively to the osteoblast lineage. The objective of this study was to examine the feasibility of using ex vivo Runx2 gene transfer to enhance the osteogenic activity of MSCs. Primary MSCs isolated from C57BL6 mice were transduced with adenoviral vectors encoding beta-galactosidase or Runx2. Cells transduced with Ad-Runx2 expressed Runx2 protein and underwent osteoblast differentiation as measured by increases in alkaline phosphatase activity and mineralization. Time-course studies revealed that Runx2 protein was highest 1 day after transduction and declined below the limits of detection by 15 days. Osteoblast marker mRNA expression paralleled Runx2 levels. In contrast, Runx2-dependent mineralization persisted for the duration of the experiment. To assess in vivo osteogenic activity, Ad-Runx2-transduced and control MSCs were adsorbed to two different carrier scaffolds and subcutaneously implanted into C57BL6 mice. In both cases, MSCs expressing Runx2 formed substantially more bone than cells transduced with control virus. Taken together, these studies indicate that Runx2 gene transfer may be an effective route to enhance the osteogenic potential of MSCs.
...
PMID:Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo. 1604 96

Fate maps based on quail-chick grafting of avian cephalic neural crest precursors and paraxial mesoderm cells have identified the majority of derivatives from each population but have not unequivocally resolved the precise locations of and population dynamics at the interface between them. The relation between these two mesenchymal tissues is especially critical for the development of skeletal muscles, because crest cells play an essential role in their differentiation and subsequent spatial organization. It is not known whether myogenic mesoderm and skeletogenic neural crest cells establish permanent relations while en route to their final destinations, or later at the sites where musculoskeletal morphogenesis is completed. We applied beta-galactosidase-encoding, replication-incompetent retroviruses to paraxial mesoderm, to crest progenitors, or at the interface between mesodermal and overlying neural crest as both were en route to branchial or periocular regions in chick embryos. With respect to skeletal structures, the results identify the avian neural crest:mesoderm boundary at the junction of the supraorbital and calvarial regions of the frontal bone, lateral to the hypophyseal foramen, and rostral to laryngeal cartilages. Therefore, in the chick embryo, most of the frontal and the entire parietal bone are of mesodermal, not neural crest, origin. Within paraxial mesoderm, the progenitors of each lineage display different behaviors. Chondrogenic cells are relatively stationary and intramembranous osteogenic cells move only in transverse planes around the brain. Angioblasts migrate invasively in all directions. Extraocular muscle precursors form tightly aggregated masses that en masse cross the crest:mesoderm interface to enter periocular territories, while branchial myogenic lineages shift ventrally coincidental with the movements of corresponding neural crest cells. En route to the branchial arches, myogenic mesoderm cells do not maintain constant, nearest-neighbor relations with adjacent, overlying neural crest cells. Thus, progenitors of individual muscles do not establish stable, permanent relations with their connective tissues until both populations reach the sites of their morphogenesis within branchial arches or orbital regions.
...
PMID:Spatial relations between avian craniofacial neural crest and paraxial mesoderm cells. 1639 89

Bone marrow-derived mesenchymal stem cells (BMDMSC) hold promise for targeted osteogenic differentiation and can be augmented by delivery of genes encoding bone morphogenetic proteins (BMP). The feasibility of promoting osteogenic differentiation of BMDMSC was investigated using two BMP genes in monolayer and three-dimensional alginate culture systems. Cultured BMDMSC were transduced with E1-deleted adenoviral vectors containing either human BMP2 or BMP6 coding sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2% alginate beads for 22 days. Adenovirus (Ad)-BMP-2 and Ad-BMP-6 transduction resulted in abundant BMP-2 and BMP-6 mRNA and protein expression in monolayer culture and BMP-2 protein expression in alginate cultures. Ad-BMP-2 and Ad-BMP-6 transduced BMDMSC in monolayer had earlier and robust alkaline phosphatase-positive staining and mineralization and were sustained for a longer duration with better morphology scores than untransduced or Ad-beta-galactosidase-transduced cells. Ad-BMP-2- and, to a lesser degree, Ad-BMP-6-transduced BMDMSC suspended in alginate demonstrated greater mineralization than untransduced cells. Gene expression studies at day 2 confirmed an inflammatory response to the gene delivery process with upregulation of interleukin 8 and CXCL2. Upregulation of genes consistent with response to BMP exposure and osteogenic differentiation, specifically endochondral ossification and extracellular matrix proteins, occurred in BMP-transduced cells. These data support that transduction of BMDMSC with Ad-BMP-2 or Ad-BMP-6 can accelerate osteogenic differentiation and mineralization of stem cells in culture, including in three-dimensional culture. BMP-2-transduced stem cells suspended in alginate culture may be a practical carrier system to support bone formation in vivo. BMP-6 induced a less robust cellular response than BMP-2, particularly in alginate culture.
...
PMID:Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6. 1664 80

The mammalian securin, pituitary tumor-transforming gene (Pttg), regulates sister chromatid separation during mitosis. Mice deficient in Pttg expression exhibit organ-specific hypoplasia of the testis, spleen, pituitary, and postmaturity pancreatic beta-cells, pointing to a possible adult stem cell defect. Bone marrow stem cells (BMSCs) contribute to bone, cartilage, and fat tissue repair and regeneration, and multipotent adult progenitor cells (MAPCs) have broader differentiation ability. Bone marrow cells derived under MAPC conditions are involved in a spectrum of tissue repair. We therefore tested whether Pttg deletion affects stem cell proliferation and differentiation. BMSCs were isolated under MAPC conditions, although unlike MAPCs, wild-type (WT) and Pttg(-/-) BMSCs do not express octamer-binding transcription factor 4 and are stem cell antigen-I positive. WT and Pttg(-/-) cells did not differ in their ability to differentiate into adipogenic, osteogenic, or hepatocyte-like cells or in phenotypic markers. Cells underwent >100 population doublings, with no observed transforming events. Pttg-null BMSCs replicated 27% slower than WT BMSCs, and under hypoxic conditions, this difference widened. Although apoptosis was not enhanced in Pttg(-/-) cells, Pttg(-/-) BMSC senescence-associated beta-galactosidase activity was elevated, consistent with enhanced p21 protein levels. Using gene array assays, DNA repair genes were shown to be upregulated in Pttg(-/-) BMSCs, whereas genes involved in cell cycle progression, including cyclin D(1), were decreased. Separase, the protease regulated by Pttg, has been implicated in DNA damage repair and was downregulated in Pttg(-/-) BMSCs. Separase was constitutively phosphorylated in Pttg(-/-) cells, a modification likely serving as a compensatory mechanism for Pttg deletion. The results indicate that Pttg deletion reduces BMSC proliferation, renders cells more sensitive to hypoxia, and enhances senescent features, thus pointing to a role for Pttg in the maintenance and proliferation of BMSCs.
...
PMID:Discordant proliferation and differentiation in pituitary tumor-transforming gene-null bone marrow stem cells. 1762 43

Arterial calcification is common in patients with type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and other chronic inflammatory disorders. Arterial calcification is associated with significant morbidity and increased early mortality. The molecular signature of vascular calcification in diabetes is strikingly similar to that of CKD. Low-grade arterial inflammation is common to both conditions, and increased levels of tumor necrosis factor-alpha (TNF-alpha) have been reported in both DM and CKD. Recently, we described a novel TNF-alpha regulated Msx2-Wnt osteogenic program that regulates arterial calcification in an animal model of type 2 DM. TNF-alpha induces the osteogenic bone morphogenetic protein-2 (BMP-2), Msx2, Wnt3a, and Wnt7a mRNAs and leads to increased aortic calcium accumulation. Treatment with the TNF-alpha neutralizing antibody infliximab abrogates aortic BMP-2-Msx2-Wnt3a and Wnt7a signaling and attenuates aortic calcium accumulation significantly. Mice with vascular TNF-alpha augmented by the SM22-TNF-alpha transgene upregulate the aortic Msx2-Wnt3a/Wnt7a axis. Furthermore, SM22-TNF-alphaTg;TOPGAL mice exhibit greater beta-galactosidase reporter staining versus TOPGAL siblings in the aorta and coronaries, which indicates enhanced mural Wnt signaling in response to TNF-alpha. Thus, inflammatory TNF-alpha signals promote aortic osteogenic Msx2-Wnt programs in type 2 DM, and arterial calcification in this model is a TNF-alpha-driven Wnt-opathy. Having established the role of TNF-alpha in diabetic vascular calcification, an unmet need exists to evaluate the role of TNF-alpha and Msx2-Wnt signals in CKD-related calcification models. If validated in these models, then these findings will have significant therapeutic applications.
...
PMID:Arterial calcification: a tumor necrosis factor-alpha mediated vascular Wnt-opathy. 1843 4

Msx2 is a homeodomain transcription factor first identified in craniofacial bone and human femoral osteoblasts. We hypothesized that Msx2 might activate skeletal Wnt signaling. Therefore, we analyzed the effects of CMV-Msx2 transgene (Msx2Tg) expression on skeletal physiology and composition. Skeletal Msx2 expression was increased 2-3-fold by Msx2Tg, with expanded protein accumulation in marrow, secondary ossification centers, and periosteum. Microcomputed tomography established increased bone volume in Msx2Tg mice, with increased numbers of plate-like trabeculae. Histomorphometry revealed increased bone formation in Msx2Tg mice versus non-Tg siblings, arising from increased osteoblast numbers. While decreasing adipogenesis, Msx2Tg increased osteogenic differentiation via mechanisms inhibited by Dkk1, an antagonist of Wnt receptors LRP5 and LRP6. Bone from Msx2Tg mice elaborated higher levels of Wnt7 canonical agonists, with diminished Dkk1, changes that augment canonical signaling. Analysis of non-Tg and Msx2Tg siblings possessing the TOPGAL reporter confirmed this; Msx2Tg up-regulated skeletal beta-galactosidase expression (p </= 0.01), along with Wnt7a and Wnt7b, and reduced circulating Dkk1. To better understand molecular mechanisms, we studied C3H10T1/2 osteoprogenitor cells. As in bone, Msx2 increased Wnt7 genes and down-regulated Dkk1, while inducing the osteoblast gene alkaline phosphatase. Msx2-directed RNA interference increased Dkk1 expression and promoter activity, while reducing Wnt7a, Wnt7b, and alkaline phosphatase. Moreover, Msx2 inhibited Dkk1 promoter activity and reduced RNA polymerase association with Dkk1 chromatin. RNA interference-mediated knockdown of Wnt7a, Wnt7b, and LRP6 significantly reduced Msx2-induced alkaline phosphatase. Msx2 exerts bone anabolism in part by reducing Dkk1 expression and enhancing Wnt signaling, thus promoting osteogenic differentiation of skeletal progenitors.
...
PMID:Msx2 exerts bone anabolism via canonical Wnt signaling. 1848 99


<< Previous 1 2 3 Next >>

---