Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone resorption plays an important role in bone modeling and remodeling. Osteoclasts are the cells responsible for the bone resorption. Osteoclasts are located on endosteal bone surfaces and on the periosteal surface beneath the periosteum. They are multinucleated giant cells highly polarized in their morphology and function. Among the proximal surface, the membrane and the area of the cytoplasm directly oppose to the bone surface, which are specialized into two regions. A central region consisting of many irregular cytoplasmic processes and infoldings, the ruffled border, is known to be the active site of bone resorption. Surrounding the ruffled border, a second region, the clear zone provides an area of close attachment to the mineralized bone surface. The osteoclasts secrete a large amount of protons by the action of H(+)-pump on the ruffled border into the sealed resorption cavity, resulting in the acidified microenvironment under which condition the bone matrix is dissolved. Protons are provided by the intracellular action of carbonic anhydrase. Following the secretion of the protons, several ion-transporting systems, i.e., carbonate-chloride exchanger, chloride-channel, Ca(2+)-transport systems, Na+/K(+)-ATPase, and voltage-dependent Ca(2+)-channel, are sequentially operated on both apical and basolateral cytoplasmic membranes. In addition, osteoclasts contain a large amount of lysosomal enzymes (cathepsin C, beta-glycerophosphatase, beta-glucuronidase, etc.), which contribute to degrade the bone organic matrices exposed in the resorption cavity. These enzymes bind to the mannose-6-phosphate receptor on Golgi apparatus, are transported to the ruffled border and are secreted into the extracellular compartment in an exocytotic manner. Osteoclasts also have a high tartrate-resistant acid phosphatase activity which is currently used as a marker enzyme osteoclastic differentiation. Osteoclasts are considered to develop from hematopoietic stem cells. So far, the following four different pathways of the differentiation of osteoclast are proposed: The precursors of osteoclast develop (1) from multilineage hematopoietic cells via a completely separate differentiation line, (2) from granulocyte macrophage-colony forming cells, (3) from committed but proliferative monocyte-macrophage, and (4) from mature and unproliferative monocyte-macrophage. However, the differentiation line of the osteoclasts has still to be elucidated. The formation of osteoclasts as well as that of other hematopoietic cells is strongly regulated by many cytokines [interleukin (IL)-1,IL-3,IL-6, M-colony stimulating factor (CSF), and GM-CSF]. 1,25-Dihydroxyvitamin D3 and parathyroid hormone also stimulate the differentiation of osteoclast precursors. However, the mature osteoclasts do not possess the receptors for these hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Osteoclasts in bone metabolism]. 175 56

In this work the biocompatibility of porous bioceramic implanted to the rabbit femoral bone was studied. The animals were killed 3, 6, 9, 14, 18 and 30 days after implantation and the callus with surrounding periosteum from the site of implant was taken for the studies. Morphological investigations of the callus were carried out up to the 30th day of healing of the bone tissue. Moreover, acid mucopolysaccharides level and activity of enzymes (acid and alkaline phosphatase, aminopeptidase, non-specific alpha-esterase, adenosine triphosphatase and succinate dehydrogenase) were studied up to the 18 day of the callus development. The results show that after bioceramic implantation, morphology of particular stages of the callus development, behaviour of acid mucopolysaccharides as well as localization and activity of enzymes are the same as in the normal healing process of the injured bone tissue. After 30 days total union of the mature bone tissue with bioceramic was established. We conclude that porous bioceramic satisfies the requirements for biomedical materials and may be safely used in the treatment of certain bone system diseases in humans.
 ...
PMID:Application of porous bioceramic in experimental therapy of bone injuries. III. Dynamics of the callus development at the site of porous bioceramic implantation. Morphological, histochemical and histoenzymological studies. 323 60

Inside-out vesicles were prepared from the plasma membrane of osteoblasts which had been isolated from the periosteum of 2-3-week-old chicken tibia and cultured for 6-8 days. Calcium uptake was initiated by adding 0.4 mM ATP and detected as a reduction in fluorescence from the reaction medium using the Ca(2+)-specific fluoroprobe, fluo-3. The reaction medium contained ouabain (1 mM) to block Na+, K(+)-ATPase activity and oligomycin (20 micrograms/ml) to block mitochondrial activity. Thapsigargin (5 microM) had little effect, indicating that contributions to Ca2+ uptake by endoplasmic reticulum derived microsomes were minimal. The Ca2+ uptake rate was 9.9 +/- 2.3 nmol/mg protein/min. Trifluoperazine (0.1 mM), which impairs the capacity of calmodulin to activate Ca(2+)-ATPase, substantially inhibited transport, as did quercetin (10 mM) and vanadate (10 microM), inhibitors of Ca(2+)-ATPases. This study has shown the presence of an outwardly directed, calmodulin-sensitive calcium transport system in the primary osteoblast plasma membrane. The pumping rate is substantially less than rates found in the intestine, a tissue which is involved in massive transport of Ca2+, but is similar to rates found in many other tissues. It is concluded that the enzyme does not support calcium translocation to sites of mineralization.
 ...
PMID:Characterization of calcium efflux by osteoblasts derived from long bone periosteum. 766 10

The contribution of vacuolar H+-ATPases (V-ATPases) to collagen degradation was investigated in soft connective tissue explants (periosteum). Immunolocalisation showed faint to intense staining of cells throughout the periosteum. The V-ATPase inhibitors, bafilomycin A1 and folimycin, decreased overall collagen degradation by 40 and 50% after 24 and 48 h, respectively. The participation of V-ATPases in intracellular degradation of collagen was demonstrated by the decrease of the amount of phagocytosed collagen in fibroblasts upon inhibition of pump activity. The inhibition of degradation was not due to a reduction in activity of gelatinase A, an enzyme previously found to mediate collagen degradation, as assessed by zymographic analysis of tissue and conditioned medium. Bafilomycin A1 even induced an increase of gelatinase A and B levels in both fractions. In conclusion, acidification by V-ATPases may represent an important mechanism in extracellular and intracellular collagen degradation in soft connective tissue.
 ...
PMID:Involvement of V-ATPases in the digestion of soft connective tissue collagen. 979 91

Metabolic oxidative stress has been implicated as a cause of osteocyte apoptosis, an essential step in triggering bone remodeling. However, little is known about the oxidative behavior of osteocytes in vivo. We assessed the redox status and distribution of total and active mitochondria in osteocytes of mouse metatarsal cortical bone in situ. Multiphoton microscopy (MPM) was used to measure fluorescence of reduced pyridine nucleotides (NADH) under normoxic conditions and acutely following extreme (postmortem) hypoxic stress. Under non-hypoxic conditions, osteocytes exhibited no detectable fluorescence, indicating rapid NADH re-oxidation. With hypoxia, NADH levels peaked and returned to near baseline levels over 3h. Cells near the periosteal surface reached maximum NADH levels twice as rapidly as osteocytes near the mid-cortex, due to the time required to initiate NADH accumulation; once started, NADH accumulation followed a similar exponential relationship at all sites. Osteocytes near periosteal and endosteal bone surfaces also had higher mitochondrial content than those in mid-cortex based on immunohistochemical staining for mitochondrial ATPase-5A (Complex V ATPase). The content of active mitochondria, assessed in situ using the potentiometric dye TMRM, was also high in osteocytes near periosteum, but low in osteocytes near endocortical surfaces, similar to levels in mid-cortex. These results demonstrate that cortical osteocytes maintain normal oxidative status utilizing mainly aerobic (mitochondrial) pathways but respond to hypoxic stress differently depending on their location in the cortex, a difference linked to mitochondrial content. An apparently high proportion of poorly functional mitochondria in osteocytes near endocortical surfaces, where increased apoptosis mainly occurs in response to bone remodeling stimuli, further suggest that regional differences in oxidative function may in part determine osteocyte susceptibility to undergo apoptosis in response to stimuli that trigger bone remodeling.
 ...
PMID:Regional differences in oxidative metabolism and mitochondrial activity among cortical bone osteocytes. 2726 Jun 46