Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.3.13 (lysyl oxidase)
 1,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated that dried plums which contain high amounts of polyphenols can restore bone mass and structure, and significantly increase indices of bone formation. The purpose of this study was to determine how dried plum polyphenols influence osteoblast activity and mineralized nodule formation under normal and inflammatory conditions. MC3T3-E1 cells were plated and pretreated with dried plum polyphenols (0, 2.5, 5, 10 and 20 microg/ml) and 24 h later stimulated with TNF-alpha (0 or 1.0 ng/ml). The 5, 10 and 20 microg/ml doses of polyphenols significantly increased intracellular ALP activity under normal conditions at 7 and 14 days, and restored the TNF-alpha-induced suppression of intracellular ALP activity by 14 days (P<.001). Polyphenols also increased mineralized nodule formation under normal and inflammatory conditions. In the absence of TNF-alpha, 5 microg/ml of polyphenols significantly up-regulated the growth factor, IGF-I, compared to controls, and the 5 and 10 microg/ml doses increased the expression of lysyl oxidase involved in collagen crosslinking. TNF-alpha decreased the expression of Runx2, Osterix and IGF-I, and polyphenols restored their mRNA levels to that of the controls. Although TNF-alpha failed to alter lysyl oxidase at 18 h, the polyphenols up-regulated its expression (P<.05) in the presence of TNF-alpha. As expected, TNF-alpha up-regulated RANKL mRNA and polyphenols suppressed RANKL expression without altering OPG. Based on these findings, we conclude that dried plum polyphenols enhance osteoblast activity and function by up-regulating Runx2, Osterix and IGF-I and increasing lysyl oxidase expression, and at the same time attenuate osteoclastogenesis signaling.
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PMID:Dried plum polyphenols attenuate the detrimental effects of TNF-alpha on osteoblast function coincident with up-regulation of Runx2, Osterix and IGF-I. 1849 59

We previously demonstrated that bovine epiphyseal chondrocytes separated by density gradient centrifugation differ in proliferative response to IGF-I and IGF-I receptor number. To identify novel modifiers of IGF-I action at the growth plate, we used microarray analyses to compare bovine hypertrophic and reserve zones and identified several receptors differentially expressed across the growth plate: NTRK2 [receptor for brain-derived neurotrophic factor (BDNF)], KIT [receptor for stem cell factor (SCF)], and MER and AXL [two receptors for growth arrest-specific 6 (Gas6)]. The corresponding ligands were tested for their ability to stimulate either proliferation of isolated chondrocytes or differentiation in ATDC5 cells. Each factor inhibited IGF-I-mediated proliferation in isolated chondrocytes by attenuating ERK1/2 activation. SCF, BDNF, Gas6, and C-type natriuretic peptide promoted differentiation in ATDC5 cells, each factor producing different expression patterns for collagen X, collagen 2, aggrecan, and lysyl oxidase. Whereas multiple factors stimulated ATDC5 differentiation, only IGF-I and high-dose insulin, out of several factors implicated in chondrocyte maturation, stimulated proliferation of isolated chondrocytes. IGF-I appears to be the primary proliferative signal in growth plate chondrocytes, whereas multiple factors including SCF, BDNF, and Gas6 regulate the pace of differentiation at the growth plate.
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PMID:SCF, BDNF, and Gas6 are regulators of growth plate chondrocyte proliferation and differentiation. 1989 99