Hayman ARTartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity 41: 218-223

School of Clinical Veterinary Science, University of Bristol, Bristol, UK.
Autoimmunity (Impact Factor: 2.71). 05/2008; 41(3):218-23. DOI: 10.1080/08916930701694667
Source: PubMed


Tartrate-resistant acid phosphatase (TRAP), once considered to be just a histochemical marker of osteoclasts is now recognised to be a molecule of widespread occurrence with functions in both the skeleton and the immune system. TRAP is expressed by osteoclasts, macrophages, dendritic cells and a number of other cell types. It has a critical role in many biological processes including skeletal development, collagen synthesis and degradation, the mineralisation of bone, cytokine production by macrophages and dendritic cells, macrophage recruitment, dendritic cell maturation and a role in the development of Th1 responses. TRAP is able to degrade skeletal phosphoproteins including osteopontin (OPN), identical to the T-cell cytokine, Eta-1. In this review, we discuss the role of TRAP in bone and immune cells and suggest that TRAP may be implicated in autoimmune disorders regulated by Th1 inflammatory responses as well as certain cancers.

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    • "To discover novel inhibitors from EAME we did screening of osteoclast by staining TRAP activity which is involved in the bone resorption process of mature osteoclast. TRAP is considered a histochemical marker of osteoclasts and is highly expressed in osteoclasts in normal condition [36]. EAME significantly reduced the RANKL induced osteoclast formation. "
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    ABSTRACT: Marine molluscs are widely distributed throughout the world and many bioactive compounds exhibiting antiviral, antitumor, antileukemic, and antibacterial activity have been reported worldwide. The present study was designed to investigate the beneficial effect of methanol extract of Euchelus asper (EAME) on estrogen deficiency induced osteoporosis in ovariectomised mice model. Forty-two female Swiss albino mice were randomly assigned into Sham operated (Sham) group and six ovariectomised (OVX) subgroups such as OVX with vehicle (OVX); OVX with estradiol (2 mg/kg/day); OVX with EAME of graded doses (25, 50, 100, and 200 mg/kg/day). Bone turnover markers like serum alkaline phosphatase (ALP), serum acid phosphatase (ACP), serum calcium, and histological investigations of tibia and uterus were analysed. Metaphyseal DNA content of the femur bone was also studied. Antiosteoclastogenic activity of EAME was examined. Administration of EAME was able to reduce the increased bone turnover markers in the ovariectomised mice. Histomorphometric analysis revealed an increase in bone trabeculation and restoration of trabecular separation by EAME treatment. Metaphyseal DNA content of the femur of the OVX mice was increased by EAME administration. EAME also showed a potent antiosteoclastogenic behaviour. Thus, the present study reveals that EAME was able to successfully reduce the estrogen deficiency induced bone loss.
    Journal of Osteoporosis 06/2014; 2014:348189. DOI:10.1155/2014/348189
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    • "Atp6v0d2 null mice exhibit osteopetrosis also called the “stone bone” disease [35], [36]. Tartrate-Resistant Acid Phosphatase 5, (ACP5) or Tartrate-Resistant Acid ATPase (TRAP) is produced and secreted by activated macrophages including osteoclasts and can catalyze the generation of reactive oxygen species (ROS), mediate iron transport and dephosphorylate osteopontin [37]. Acp5 knockout mice have mild osteoporosis [38]. "
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    ABSTRACT: Cigarette smoke is well known for its adverse effects on human health, especially on the lungs. Basic research is essential to identify the mechanisms involved in the development of cigarette smoke-related diseases, but translation of new findings from pre-clinical models to the clinic remains difficult. In the present study, we aimed at comparing the gene expression signature between the lungs of human smokers and mice exposed to cigarette smoke to identify the similarities and differences. Using human and mouse whole-genome gene expression arrays, changes in gene expression, signaling pathways and biological functions were assessed. We found that genes significantly modulated by cigarette smoke in humans were enriched for genes modulated by cigarette smoke in mice, suggesting a similar response of both species. Sixteen smoking-induced genes were in common between humans and mice including six newly reported to be modulated by cigarette smoke. In addition, we identified a new conserved pulmonary response to cigarette smoke in the induction of phospholipid metabolism/degradation pathways. Finally, the majority of biological functions modulated by cigarette smoke in humans were also affected in mice. Altogether, the present study provides information on similarities and differences in lung gene expression response to cigarette smoke that exist between human and mouse. Our results foster the idea that animal models should be used to study the involvement of pathways rather than single genes in human diseases.
    PLoS ONE 03/2014; 9(3):e92498. DOI:10.1371/journal.pone.0092498 · 3.23 Impact Factor
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    • "Development of both PsA and RA is frequently accompanied by bone erosion due to osteoclast activation and increased synthesis of collagenolytic proteinases (22,23). Morphometric analysis of tartrate-resistant acid phosphatase (TRAP)–positive tissue in the distal phalanges as a marker of activated osteoclasts and monocytes showed a clear increase in TRAP expression during the time of doxycycline treatment, and as with other signs of TNFα-mediated inflammation in this organ, TRAP expression reverted to control levels after removal of the antibiotic (Figure 5B). "
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    ABSTRACT: Objective To generate doxycycline-inducible human tumor necrosis factor α (TNFα)–transgenic mice to overcome a major disadvantage of existing transgenic mice with constitutive expression of TNFα, which is the limitation in crossing them with various knockout or transgenic mice. MethodsA transgenic mouse line that expresses the human TNFα cytokine exclusively after doxycycline administration was generated and analyzed for the onset of diseases. ResultsDoxycycline-inducible human TNFα–transgenic mice developed an inflammatory arthritis– and psoriasis-like phenotype, with fore and hind paws being prominently affected. The formation of “sausage digits” with characteristic involvement of the distal interphalangeal joints and nail malformation was observed. Synovial hyperplasia, enthesitis, cartilage and bone alterations, formation of pannus tissue, and inflammation of the skin epidermis and nail matrix appeared as early as 1 week after the treatment of mice with doxycycline and became aggravated over time. The abrogation of human TNFα expression by the removal of doxycycline 6 weeks after beginning stimulation resulted in fast resolution of the most advanced macroscopic and histologic disorders, and 3–6 weeks later, only minimal signs of disease were visible. Conclusion Upon doxycycline administration, the doxycycline-inducible human TNFα–transgenic mouse displays the major features of inflammatory arthritis. It represents a unique animal model for studying the molecular mechanisms of arthritis, especially the early phases of disease genesis and tissue remodeling steps upon abrogation of TNFα expression. Furthermore, unlimited crossing of doxycycline-inducible human TNFα–transgenic mice with various knockout or transgenic mice opens new possibilities for unraveling the role of various signaling molecules acting in concert with TNFα.
    Arthritis & Rheumatology 09/2013; 65(9). DOI:10.1002/art.38026 · 7.76 Impact Factor
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