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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aryl hydrocarbon receptor (AhR) ligands are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototypical compound is TCDD (2,3,7, 8-tetrachlorodibenzo-p-dioxin), also known as dioxin. There is an increasing body of knowledge linking cigarette smoking to osteoporosis and periodontal disease, but the direct effects of smoke-associated aryl hydrocarbons on bone are not well understood. Through the use of resveratrol (3,5,4'-trihydroxystilbene), a plant antifungal compound that we have recently demonstrated to be a pure AhR antagonist, we have investigated the effects of TCDD on osteogenesis. It was postulated that TCDD would inhibit osteogenesis in bone-forming cultures and that this inhibition would be antagonized by resveratrol. We employed the chicken periosteal osteogenesis (CPO) model, which has been shown to form bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo, as well as a rat stromal cell bone nodule formation model. In the CPO model, alkaline phosphatase (AP) activity was reduced by up to 50% (P<0.01 vs control) in the presence of 10(-9) M TCDD and these effects were reversed by 10(-6) M resveratrol (P<0.05 vs TCDD alone). TCDD-mediated inhibition of osteogenesis was restricted primarily to the osteoblastic differentiation phase (days 0-2) as later addition did not appear to have any effects. Message levels for important bone-associated proteins (in the CPO model) such as collagen type I, osteopontin, bone sialoprotein and AP were inhibited by TCDD, an effect that was antagonized by resveratrol. Similar findings were obtained using the rat stromal bone cell line. TCDD (at concentrations as low as 10(-10)M) caused an approximately 33% reduction in AP activity, which was abrogated by 3. 5x10(-7) M resveratrol. TCDD also induced a marked reduction in mineralization ( approximately 75%) which was completely antagonized by resveratrol. These data suggest that AhR ligands inhibit osteogenesis probably through inhibition of osteodifferentiation and that this effect can be antagonized by resveratrol. Since high levels of AhR ligands are found in cigarette smoke, and further since smoking is an important risk factor in both osteoporosis and periodontal disease, it may be postulated that AhR ligands are the component of cigarette smoke linking smoking to osteoporosis and periodontal disease. If so, resveratrol could prove to be a promising preventive or therapeutic agent for smoking-related bone loss.
...
PMID:Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol. 1198 Apr 60

We have investigated the expression and synthesis of potential bone-resorbing cytokines, interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor (TNF) in rheumatoid arthritic (RA) and osteoarthritic (OA) bone, two common diseases which are associated with bone loss. Primary human osteoblast (hOB) cultures were established to determine the temporal mRNA expression of IL-6, IL-1 (alpha and beta), and TNF (alpha and beta) in relation to osteoblast growth and phenotypic genes. IL-6 mRNA levels were found to be significantly higher (P < 0.04) in both OA hOB (17 patients) and RA hOB (10 patients) compared to normal (NO) hOB (9 patients) and reached five-fold increases in OA hOB and 13-fold increases in RA hOB. Maximal levels of IL-6 are expressed at Day 21 which corresponds to the mineralization stage reflected by decreasing collagen I (alpha(1)), osteopontin, bone sialoprotein, alkaline phosphatase mRNA levels, while osteocalcin (OC) mRNA levels increased. IL-6 protein levels also were significantly higher (P < 0.05) in OA hOB and RA hOB compared to NO hOB. These increases were not attributable to sex or age of the donor bone. Neither the mRNA encoding IL-1(alpha and beta) and TNF(alpha and beta) nor the related proteins were detectable. These results indicate that differentiated OA hOB and RA hOB within a bone tissue-like matrix constitutively express and secrete high levels of IL-6. This inherent property suggests that these osteoblasts, independent of local inflammatory parameters, can contribute to enhanced recruitment of osteoclast progenitors and thereby bone resorption.
...
PMID:Increased mRNA expression and protein secretion of interleukin-6 in primary human osteoblasts differentiated in vitro from rheumatoid and osteoarthritic bone. 1132 21

The expression of hard tissue associated proteins may be used to identify periodontal fibroblasts with the capability to facilitate periodontal regeneration. The aim of this study was to describe, by immunohistochemistry, the distribution of osteocalcin, osteopontin, bone sialoprotein and bone morphogenic proteins-2 and -4 (BMP-2 and BMP-4) within the human periodontium. Furthermore, the expression of mRNA for the above proteins and alkaline phosphatase by gingival and periodontal ligament fibroblasts in vitro was also assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Localization of osteopontin, osteocalcin, BMP-2 and BM P-4 within sections of human periodontal structures was stronger in the periodontal ligament compared to the gingiva. Bone sialoprotein was not detected in either of the soft tissues but, along with osteopontin and osteocalcin, it was localized in the cementum and bone. In vitro, both the gingival and periodontal ligament fibroblasts expressed mRNA for alkaline phosphatase, BMP-2, BMP-4 and osteopontin. Although there were no differences in the expression of alkaline phosphatase and BMP-4 mRNA between the two cell types, we noted significantly higher mRNA levels of osteopontin in the periodontal ligament and BM P-2 in the gingival fibroblasts. Osteocalcin and bone sialoprotein mRNA expression was only noted in the cultured periodontal ligament fibroblasts. From these results, it can be concluded that distinct differences exist between the two fibroblast populations in terms of the localization and mRNA expression of the majority of the hard tissue associated proteins. Furthermore, the elevated in vitro mRNA expression for osteocalcin, osteopontin and bone sialoprotein may be used to identify cells with the potential to facilitate hard tissue formation and hence periodontal regeneration.
...
PMID:Expression of bone associated macromolecules by gingival and periodontal ligament fibroblasts. 1145 11

In dentinogenesis, certain growth factors, matrix proteoglycans, and proteins are directly or indirectly dependent on growth hormone. The hypothesis that growth hormone up-regulates the expression of enzymes, sialoproteins, and other extracellular matrix proteins implicated in the formation and mineralization of tooth and bone matrices was tested by the treatment of Lewis dwarf rats with growth hormone over 5 days. The molar teeth were processed for immunohistochemical demonstration of bone-alkaline phosphatase, bone morphogenetic proteins-2 and -4, osteocalcin, osteopontin, bone sialoprotein, and E11 protein. Odontoblasts responded to growth hormone by more cells expressing bone morphogenetic protein, alkaline phosphatase, osteocalcin, and osteopontin. No changes were found in bone sialoprotein or E11 protein expression. Thus, growth hormone may stimulate odontoblasts to express several growth factors and matrix proteins associated with dentin matrix biosynthesis in mature rat molars.
...
PMID:Growth-hormone-stimulated dentinogenesis in Lewis dwarf rat molars. 1166 86

We report the establishment in vitro of three-dimensional (3D) cultures of human osteoblasts (hOB) derived from normal adults and supported uniquely by the extracellular matrix (ECM) they deposit. Osteoblasts were cultured in 3D cultures in vitro for up to 120 days. The 3D cultures, examined at 25, 31, and 48 days, expressed protein markers of osteoblastic cells, namely osteonectin, collagen type I, fibronectin, osteopontin, bone sialoprotein, biglycan, and decorin. Sequentially, alkaline phosphatase (AP) and then Ca incorporation, mineralization of matrix (monitored by histochemistry and transmission electron microscopy), and finally osteocalcin expression, were detected in the 3D cultures. Ultrastructurally, morphology progressed from early to mature osteoblast and to osteocyte-like. Cells were embedded in a matrix with organized collagen type I fibers containing, increasingly with time of culture, needle-shaped crystals, often associated with matrix vesicles, characteristic of those in bone. During the culture (up to 120 days) there was an outgrowth of proliferating osteogenic cells from the 3D structure. Subcutaneous implantation in nude mice for 20 days of osteoblasts cultured in 3D culture for different lengths of time in vitro, showed progression of mineralization from the inner region of the implant outward, with peripheral cells being embedded in nonmineralized, collagen-rich matrix. The 3D implants were invaded by vessels derived from the host.
...
PMID:Three-dimensional cultures of normal human osteoblasts: proliferation and differentiation potential in vitro and upon ectopic implantation in nude mice. 1199 10

Diabetes is associated with an increased prevalence of atherosclerotic vascular disease and cardiovascular mortality. In diabetic patients, medial calcification appears to be a strong independent predictor of cardiovascular mortality, it occurs particularly in those with neuropathy. Recent evidence suggests that medial calcification in diabetes is an active, cell-mediated process, similar to that observed in patients with end-stage renal disease (ESRD), in which vascular smooth muscle cells (VSMCs) express a number of bone matrix proteins that act to either facilitate or regulate the calcification process. Several bone-associated proteins (e.g., osteopontin, bone sialoprotein, alkaline phosphatase, type 1 collagen, osteocalcin) have been demonstrated in histologic sections of vessels obtained from patients with diabetes or ESRD. In in vitro experiments, high glucose induced cell proliferation and expression of osteopontin in cultured VSMCs. Hypoxia had additive effects of hyperglycemia on VSMCs. In addition, uremic serum upregulates osteoblast transcription factor Cbfa 1 and osteopontin expression in cultured VSMCs. The pathogenesis of vascular calcification in diabetes is not completely understood, although high glucose and other potential factors may play an important role by transforming VSMCs into osteoblast-like cells. Further understanding of the mechanism by which diabetes induces this complication is needed to design effective therapeutic strategies to intervene with this process.
...
PMID:Arterial calcification in diabetes. 1264 43

Mesenchymal stem cells give rise to osteoprogenitors that proliferate and differentiate into identifiable preosteoblasts, osteoblasts, bone lining cells and osteocytes. To identify and establish a molecular profile for the more primitive and uncharacterized cells in the lineage, relatively rare (<1%) osteoprogenitors present in primary cultures of fetal rat calvaria cell populations were identified by a replica plating technique. Since the cell number was limited in each colony sampled, we used global amplification PCR to analyze the repertoire of genes expressed in osteoprogenitors. We established a molecular fingerprint and a developmental sequence based on simultaneous expression patterns for both known osteoblast-associated markers (collagen type I, alkaline phosphatase, osteopontin, bone sialoprotein, PTH1R and osteocalcin) and potential regulatory molecules (i.e. FGFR1, PDGF-Ralpha and PTHrP). By analysis of 99 osteoprogenitor and osteoblast colonies captured by replica plating at different developmental stages, we found: (1) a recognizable cohort of cells considered more primitive than committed osteoprogenitors; (2) a cohort of early progenitors transiently expressing bone sialoprotein; and (3) that mRNAs for FGF-R1, PDGF-Ralpha and PTH1R were expressed earlier than other markers and tended to increase and decrease in relative concert with the osteoblast-specific markers. The observations suggest that within the osteoblast differentiation sequence both discrete stages and continua of changing marker expression levels occur with variation in expression for any given marker. This combined approach of replica plating and global amplification PCR allows molecular fingerprinting of definitive primitive osteoprogenitors and will aid in identifying novel developmental stages and novel differentiation stage-specific genes as these cells progress through their differentiation sequence.
...
PMID:Global amplification polymerase chain reaction reveals novel transitional stages during osteoprogenitor differentiation. 1266 59

Dialysis patients have increased cardiovascular morbidity, mortality, and vascular calcification, and the latter appears to impact the former. Recent evidence indicates that vascular calcification is an active, cell-mediated process. Osteoblast differentiation factor Cbfa1 and several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) are present in histologic sections of arteries obtained from patients with end-stage renal disease (chronic kidney disease stage V [CKD-V]). This supports the theory that vascular smooth muscle cells can dedifferentiate or transform to osteoblast-like cells, possibly by up-regulation of Cbfa1. In in vitro experiments, addition of pooled serum from dialysis patients (versus normal healthy controls) accelerated mineralization and increased expression of Cbfa1, osteopontin, and alkaline phosphatase in cultured vascular smooth muscle cells. Clinically, the pathogenesis of vascular calcification is not completely understood, although increased levels of phosphorus and/or other potential uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells. Presumably, once this process begins, increased serum calcium X phosphorus product, or calcium load from binders, accelerates this process. In addition, it is likely that circulating inhibitors of calcification are also important. Further understanding of the pathophysiology of vascular calcification is needed to intervene appropriately.
...
PMID:Vascular calcification in chronic kidney disease. 1473 May 11

Patients with chronic kidney disease (CKD) on dialysis have 2- to 5-fold more coronary artery calcification than age-matched individuals with angiographically proven coronary artery disease. In addition to increased traditional risk factors, CKD patients also have a number of nontraditional cardiovascular risk factors that may play a prominent role in the pathogenesis of arterial calcification, including duration of dialysis and disorders of mineral metabolism. In histological specimens from the inferior epigastric artery of dialysis patients, we have found expression of the osteoblast differentiation factor core binding factor alpha-1 (Cbfa1) and several bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) in both the intima and medial layers when calcification was present. In cultured vascular smooth muscle cells, the addition of pooled serum from dialysis patients (versus normal healthy controls) accelerated mineralization and increased expression of Cbfa1, osteopontin, and alkaline phosphatase to a similar magnitude as does beta-glycerophosphate alone. However, a lack of inhibitors of calcification may also be important. Dialysis patients with low levels of serum fetuin-A, a circulating inhibitor of mineralization, have increased coronary artery calcification and fetuin-A can inhibit mineralization of vascular smooth muscle cells in vitro. These data support that elevated levels of phosphorus and/or other potential uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells, which can produce a matrix of bone collagen and noncollagenous proteins. This nidus can then mineralize if the balance of pro-mineralizing factors outweighs inhibitory factors.
...
PMID:Pathophysiology of vascular calcification in chronic kidney disease. 1537 22

Recent evidence suggests that uremic vascular calcification is an active cell-mediated process resembling osteogenesis in bone rather than passive precipitation. We have identified increased expression of bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen), and the bone-specific transcription factor core-binding factor alpha-1 (Cbfa1) in histologic sections of inferior epigastric arteries obtained from patients with end-stage renal disease (ESRD) or calcific uremic arteriolopathy. In in vitro experiments, the addition of uremic serum to cultured vascular smooth muscle cells up-regulated osteopontin and Cbfa1 expression and accelerated mineralization. This implies that the uremic milieu may lead to dedifferentiation of vascular smooth muscle cells with subsequent mineralization. Further understanding of the pathophysiology of uremic vascular calcification is needed to design effective therapeutic strategies to intervene with this devastating condition in ESRD patients.
...
PMID:Uremic vasculopathy. 1549 Apr 1


<< Previous 1 2 3 4 Next >>

---