Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strong experimental evidence exists for a relationship between mast cells and bone disease, but the role of mast cells in the regulation of bone remodeling is unknown. In order to address this question, mast cell deficient mice (W/Wv) were paired with their mast cell sufficient (+/+) littermates and evaluated for differences in response to an induced cycle of bone remodeling. This was achieved using a tooth egression protocol, in which a synchronous cycle of bone remodeling was induced in the mandibular buccal alveolar periosteum by extraction of the opposing dentition. Quantitative histomorphometric changes during the activation, resorption, reversal, and formation phases of bone remodeling were documented using standard techniques. Most cell deficient mutants exhibited the following defects in response to an induced cycle of bone remodeling: (a) the onset of the remodeling cycle was delayed by a prolonged activation phase, (b) the duration and extent of the active formation phase was decreased, and (c) the amount of new bone matrix synthesized was diminished while mineralization rates were found to be normal. These results suggest that mast cells and their mediators provide a paracrine mechanism which influences the recruitment of osteoclast and osteoblast progenitors and their participation in bone remodeling. Nonetheless, since bone remodeling occurs in mast cell deficient mice, albeit less efficiently, this mechanism is most likely one of several redundant mechanisms that provide for adequate skeletal homeostasis.
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PMID:Bone remodeling in W/Wv mast cell deficient mice. 179 71

Increase in mast cell (MC) number has been reported in some pathological conditions with increased remodeling. However, it is not known whether MCs are involved in the physiological remodeling of bone. In the present study the possible variations in MCs were investigated during the activation phase in a rat model of synchronized remodeling. Seven groups of 10 rats were used. As early as the first day of induction, MCs increased by 50% and then decreased on day 2. The same pattern of changes recurred on days 3 and 4. Intact non-degranulating MCs increased mainly at some distance from the bone surface. Degranulating MCs conversely decreased near the cambium layer of the periosteum. Prostaglandins were not involved in these changes. These results suggest an association between the events leading to the onset of bone resorption and MCs. Degranulation might induce the release of agents active on these events.
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PMID:Changes in mast cell number during the activation phase of an induced synchronized remodeling sequence in the rat. 225 14

As studied by intravital microscopy, mast cell-dependent inflammatory reactions evoked by antigen or compound 48/80 in the hamster cheek pouch involved leakage of plasma and emigration of leukocytes exclusively from the venules. The leukocyte diapedesis and subsequent tissue migration induced by antigen or compound 48/80 were oriented from the venules towards adjacent arterioles. In contrast, leukocyte emigration induced by a mast cell-independent stimulus, leukotriene B4, did not show preferential orientation towards arterioles. Moreover, mast cells were abundant in the hamster cheek pouch, and they were localized predominantly along arterioles, rather than along venules. Because mast cells are considered to be the source of the chemotactic mediators causing the leukocyte emigration, the periarteriolar mast cell localization may be of functional significance by creating chemotactic gradients between arterioles and venules, thereby promoting oriented and effective interstitial migration of leukocytes. Whether or not a similar mechanism is operative in other species and tissues remains to be established, however, arteriolar predominance of mast cells was observed also in rat calvarial periosteum and in mouse skin.
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PMID:Periarteriolar localization of mast cells promotes oriented interstitial migration of leukocytes in the hamster cheek pouch. 253 21

The role of leukotrienes on bone resorption was tested in a well-standardized model of bone remodeling by inhibiting their biosynthesis with BWA4C, a specific inhibitor of 5-lipoxygenase. After extraction of their upper molars unilaterally, 30 Wistar rats were divided into three groups; the first remained untreated (control group), the second received 80 mg/kg/day of BWA4C dissolved in polyethylene glycol 300 (experimental group), and the third received only the vehicle (sham-treated group). After four days of experiment, the animals were killed and the resorption profile was assessed along the antagonist mandibular buccal cortex. The main result was a dramatic decrease in the number of TRAP-positive mononucleated preosteoclasts in the experimental group (-69%, p < 0.0005 and p < 0.003 vs. the control and sham-treated groups, respectively). This drop was related to a significant decrease in the number of osteoclasts. Neither the activation of the differentiated osteoclasts nor their mean interface with the bone surface were affected by BWA4C. Concomitantly, the mast cell population residing near the vascular network limiting the periosteum was markedly and significantly increased by the treatment. These mast cells were mostly degranulating, i.e., were in a state of activation that we previously found to related to resorption. These data suggest (1) that the leukotrienes are involved in the recruitment of osteoclast progenitors, and/or their differentiation into preosteoclasts, and (2) that mast cells responded to leukotriene inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 5-lipoxygenase inhibitor BWA4C impairs osteoclastic resorption in a synchronized model of bone remodeling. 855 28

The activation step of bone remodeling remains poorly characterized. Activation comprises determination of the site to be remodeled, osteoclast precursor recruitment, their migration to the site of remodeling, and differentiation. These actions involve different compartments and cell types. The aim of this study was to investigate events and cell types involved during activation. We used a bone remodeling model in rats where extractions of the upper jaw molars initiate remodeling of the antagonist lower jaw (mandible) cortex along the periosteum. In this model osteoclastic resorption peaks 4 days after extractions. We previously reported that mast cell activation in the periosteum fibrous compartment is an early event of activation, associated with recruitment of circulating monocyte osteoclast precursors. By using immunohistochemistry, we observed 9 hours after induction a spatially oriented expression of InterCellular Adhesion Molecule-1 in the vessels that was inhibited by antagonists of histamine receptors 1 and 2. It was followed at 12 hours by the recruitment of ED1+ monocytes. In parallel, at 9 hours, Vascular Cellular Adhesion Molecule-1+ fibroblast-like cells scattered in the fibrous compartment of the periosteum between the vessels and the osteogenic compartment increased; these cells may be implicated in osteoclast precursor migration. Receptor Activator of NF KappaB Ligand+ cells increased at 12 hours in the osteogenic compartment and reached a peak at 18 hours. At 24 hours the numbers of osteogenic cells and subjacent osteocytes expressing semaphorin 3a, a repulsive for osteoclast precursors, decreased before returning to baseline at 48 hours. These data show that during activation the two periosteum compartments and several cell types are coordinated to recruit and guide osteoclast precursors towards the bone surface.
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PMID:Coordination of early cellular reactions during activation of bone resorption in the rat mandible periosteum: An immunohistochemical study. 2922 61