Abstract:
BACKGROUND AND PURPOSE:Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing. EXPERIMENTAL APPROACH:In the present study, we investigated the effects of a monoclonal anti-Mdk antibody (Mdk-Ab) on bone healing using a standardized femur osteotomy model in mice. Additional in vitro experiments using chondroprogenitor and preosteoblastic cells were conducted to analyse the effects of recombinant Mdk and Mdk-Ab on differentiation markers and potential binding partners in these cells. KEY RESULTS:We demonstrated that treatment with Mdk-Ab accelerated bone healing in mice based on increased bone formation in the fracture callus. In vitro experiments using preosteoblastic cells showed that Mdk-Ab treatment abolished the Mdk-induced negative effects on the expression of osteogenic markers and Wnt/β-catenin target proteins, whereas the differentiation of chondroprogenitor cells was unaffected. Phosphorylation analyses revealed an important role for the low-density lipoproteinLDL receptor-related protein 6 in Mdk signalling in osteoblasts. CONCLUSIONS AND IMPLICATIONS:We conclude that Mdk-Ab treatment may be a potential novel therapeutic strategy to enhance fracture healing in patients with orthopaedic complications such as delayed healing or non-union formation.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Haffner-Luntzer M,Heilmann A,Rapp AE,Roessler R,Schinke T,Amling M,Ignatius A,Liedert Adoi
10.1111/bph.13503subject
Has Abstractpub_date
2016-07-01 00:00:00pages
2237-49issue
14eissn
0007-1188issn
1476-5381journal_volume
173pub_type
杂志文章abstract::1. In vivo microdialysis has been used to investigate the concentration of various amino acids and lactate in the extracellular fluid of the rat cortex following focal ischaemia, the probe being placed in the core of the infarct area. 2. An ischaemic infarct was produced in the cortex by use of a photochemical dye (Ro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13050.x
更新日期:1994-05-01 00:00:00
abstract::Monocytes and macrophages provide key targets for the action of novel anti-inflammatory therapeutics targeted at inhibition of PDE4 cAMP-specific phosphodiesterases. PDE4 enzymes provide the dominant cAMP phosphodiesterase activity in U937 human monocytic cells. Differentiation of U937 monocytic cells to a macrophage-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705770
更新日期:2004-05-01 00:00:00
abstract::1. We investigated whether K(+) can act as an endothelium-derived hyperpolarizing factor (EDHF) in isolated small renal arteries of Wistar-Kyoto rats. 2. Acetylcholine (0.001 - 3 microM) caused relaxations that were abolished by removal of the endothelium. However, acetylcholine-induced relaxations were not affected b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703965
更新日期:2001-04-01 00:00:00
abstract::1. The concentrations of adrenaline and noradrenaline in the brains of chickens (Gallus domesticus) have been determined using two different methods of fluorimetric analysis.2. The concentrations of adrenaline, noradrenaline and also dopamine were found to increase with age, as did the relative amount of adrenaline pr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10605.x
更新日期:1970-09-01 00:00:00
abstract::1. We investigated the hypothesis that, as in some other large human arteries, 5-HT-induced contraction of the temporal artery is mediated through two co-existing receptor populations, 5-HT1-like- and 5-HT2A. Temporal arterial segments were obtained from patients undergoing brain surgery and rings prepared set up to c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15188.x
更新日期:1996-01-01 00:00:00
abstract::Ivabradine has proven therapeutic efficacy for cardiac ischaemia and, until proved otherwise, is a very specific inhibitor of the cardiac sinoatrial node I(f) current. In the current issue of the British Journal of Pharmacology, Drouin et al. demonstrated that chronic treatment of the human apoB-100 transgene dyslipid...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.168
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abstract::1. Single smooth muscle cells were isolated from bovine trachealis by enzymic digestion. The properties of large conductance plasmalemmal K(+)-channels in these cells were studied by the patch-clamp recording technique. 2. Recordings were made from inside-out plasmalemmal patches when [K+] was symmetrically high (140 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12269.x
更新日期:1991-04-01 00:00:00
abstract::After many years of effort, recent technical breakthroughs have enabled the X-ray crystal structures of three G-protein-coupled receptors (GPCRs) (beta1 and beta2 adrenergic and adenosine A(2a)) to be solved in addition to rhodopsin. GPCRs, like other membrane proteins, have lagged behind soluble drug targets such as ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2009.00476.x
更新日期:2010-03-01 00:00:00
abstract::1. Neurotensin was infused intravenously, in the presence or absence of intravenous atropine or intraarterial tetrodotoxin, into dogs anaesthetized with sodium pentobarbitone. Net and unidirectional fluxes of sodium and blood flows in the ileum were measured. Arterial and mesenteric venous blood pressures, haematocrit...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11506.x
更新日期:1988-05-01 00:00:00
abstract::1. Piperazinylindoles (DPI 201-106, BDF 8784), drugs known to act on voltage-dependent Na(+)-channels, bind with very high affinity to a Ca2(+)-channel-associated phenylalkylamine receptor in Drosophila melanogaster head membranes. These compounds and (+)-tetrandrine, a naturally occurring Ca2(+)-antagonist, were the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12193.x
更新日期:1991-02-01 00:00:00
abstract::1. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2-purinoceptor antagonist, was investigated for its ability to antagonize: (1) P2X-purinoceptor-mediated contractions of the rabbit central ear artery and saphenous artery evoked by either alpha,beta-methylene ATP (alpha,beta-MeATP) or electrical fie...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14827.x
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Subset of macrophages within the atheroma plaque displays a high glucose uptake activity. Nevertheless, the molecular mechanisms and the pathophysiological significance of this high glucose need remain unclear. While the role for hypoxia and hypoxia inducible factor 1α has been demonstrated, the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15358
更新日期:2020-12-29 00:00:00
abstract::1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701767
更新日期:1998-04-01 00:00:00
abstract::1. The effects of some chloride channel antagonists were studied on the calcium-activated chloride current (ICl(Ca)) in smooth muscle cells from the rabbit portal vein with the perforated patch technique. 2. 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and 4,4'-diisothiocyanato-stilbene-2,2'-disu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14891.x
更新日期:1994-04-01 00:00:00
abstract::1. The mechanism of toxicity of sulphur mustard was investigated by examining the biochemical effects of the analog 2-chloroethylethyl sulphide (CEES) in both human Jurkat cells as well as normal human lymphocytes. 2. Exposure of both types of cells to CEES resulted in a marked decrease in the intracellular concentrat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705591
更新日期:2004-03-01 00:00:00
abstract::The concentrations of catecholamines and the activities of dopamine-beta-hydroxylase were measured in blood obtained from decapitated diabetic and aged-matched control rats. The activity of dopamine-beta-hydroxylase in blood from diabetic rats was much greater (5 fold) than that seen for control rats. For both diabeti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb08632.x
更新日期:1978-09-01 00:00:00
abstract::1. This study was undertaken to evaluate in vivo the influence of amiodarone on the effects of triiodothyronine (T3) in brown adipose tissue (BAT) which are independent of thyroid hormone synthesis and of the conversion of thyroxine (T4) to T3. Thyroidectomized rats were given a replacement dose of T3 (0.5 mg kg(-1) p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702456
更新日期:1999-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14465
更新日期:2018-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12275.x
更新日期:1991-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb10553.x
更新日期:1985-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Atrial fibrillation (AF) is the most common electrical cardiac disorder in clinical practice. The major trigger for AF is focal ectopic activity of unknown origin in sleeves of cardiac muscle that extend into the pulmonary veins. We examined the role of noradrenaline in the genesis of ectopic act...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707177
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01015.x
更新日期:2011-01-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09687.x
更新日期:1974-09-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14934
更新日期:2020-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12597
更新日期:2014-06-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11637.x
更新日期:1988-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07070.x
更新日期:1971-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Humanized mice for the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ), termed PPARδ knock-in (PPARδ KI) mice, were generated for the investigation of functional differences between mouse and human PPARδ and as tools for early drug efficacy assessment. EXPERIMENTAL APPROACH...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01359.x
更新日期:2011-09-01 00:00:00
abstract::1 Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) differentially activate three Y receptors (Y(1), Y(2) and Y(4)) in mouse and human isolated colon. 2 The aim of this study was to characterise Y(2) receptor-mediated responses in colon mucosa and longitudinal smooth muscle preparations from wild ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705298
更新日期:2003-06-01 00:00:00
abstract::1. The effect of a standardized mixture of beta-hydroxyethyl rutosides against oxidative damage in singlet oxygen-challenged isolated cardiac myocytes from adult rats was investigated. The morphology of the myocytes was evaluated as an indicator for cell viability (elongated, rod shaped cells vs. hypercontracted, roun...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15725.x
更新日期:1996-10-01 00:00:00