Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy.
ABSTRACT 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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ABSTRACT: Foreign body-type multinucleated giant cells (FBGC), formed by macrophage fusion, are a prominent cell type on implanted biomaterials, although the roles they play at these and other sites of chronic inflammation are not understood. Why lymphocytes are present in this scenario and the effects of fusing macrophages/FBGC on subsequent lymphocyte responses are also unclear. To address the physiological significance of FBGC in this regard, we employed our in vitro system of interleukin (IL)-4-induced human monocyte-derived macrophage fusion/FBGC formation. Initially, we pursued the identities of lymphocyte co-stimulatory molecules on fusing macrophages/FBGC. In addition, we further compared the FBGC phenotype to that currently associated with osteoclasts and dendritic cells using recognized markers. Immunoblotting of cell lysates and immunochemistry of macrophages/FBGC in situ, revealed that IL-4-induced macrophages/FBGC strongly express HLA-DR, CD98, B7-2 (CD86), and B7-H1 (PD-L1), but not B7-1 (CD80) or B7-H2 (B7RP-1). Furthermore, molecules currently recognized to be expressed on osteoclasts (calcitonin receptor, tartrate-resistant acid phosphatase, RANK) or dendritic cells (CD1a, CD40, CD83, CD95/fas) are undetectable. In contrast, fusing macrophages/FBGC strongly express the macrophage markers αX integrin (CD11c), CD68, and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), whereas CD14 is completely down-modulated with IL-4-induced macrophage fusion. These novel data demonstrate that IL-4-induction of macrophage multinucleation/FBGC formation features the acquisition of a CD14-negative phenotypic profile which is distinguishable from that of dendritic cells and osteoclasts, yet potentially exhibits multiple capacities for lymphocyte interactions with resultant lymphocyte down-modulation.Experimental and Molecular Pathology 07/2011; 91(3):673-81. DOI:10.1016/j.yexmp.2011.06.012 · 2.88 Impact Factor
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ABSTRACT: Elasmoid scales from the common carp (and other teleostean fishes) appear to be an exciting new model in the research of mineralized tissues. The presence of alkaline phosphatase (ALP), a marker of mineralization, on both sides of the scale was demonstrated by means of enzyme histochemistry. Tartrate-resistant acid phosphatase, a marker for mineral degradation and osteoclasts, was observed along the radii, at the same location as the ALP activity on the episquamal side. This points towards an active mineral metabolism, were scale cells are involved in both formation and degradation of the mineralized matrix. Cathepsin K staining revealed the presence of multinuclear osteoclasts along the grooves of the scale. Interestingly, the scales were taken from growing control fish; they were not induced to resorb their matrix. Presence of these enzymes in scale cells, together with the demineralized regions in the centre of the scale suggest a more dynamic mineral metabolism in cyprinid scales then previously observed in other species. Scales are derived from odontode tissues, their formation relies on many the same underlying mechanisms and genes as other mineralized tissues. Moreover, a single scale offers the possibility to culture scale-forming and -degrading cells together on their original matrix. All of the these unique properties substantiate the potential of scales to yield new insights on osteoclasts and regulation of tissue mineralization.Journal of Applied Ichthyology 03/2010; 26(2):210 - 213. DOI:10.1111/j.1439-0426.2010.01407.x · 0.90 Impact Factor
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ABSTRACT: _Background_ Our bones are remodelled repeatedly throughout life. New and “healthy” bone tissue replaces the old one. It has been shown that the bone degrading cells, the osteoclasts, prefer old and fatigued bone. The young bone mineral, i.e. calcium apatite, is less crystalline than the mature one. Is it possible that the osteoclasts distinguish between relatively old and new bone via its mineral crystallinity? _Methodology/Principal Findings_ Acid phosphatase is an enzyme abundantly expressed by the osteoclasts during resorption and therefore used as a marker of the cells’ activity. This study explores whether its enzymatic activity would be decreased in the presence of biomimetically prepared noncrystalline calcium phosphate and nanocrystalline bone-like calcium apatite. The results showed that both biomimetic samples decreased significantly the enzyme activity while commercially available calcium phosphate samples (hydroxyapatite and brushite) did not. Consistent with our hypothesis the noncrystalline calcium phosphate had the greater inhibition effect. _Conclusions/Significance_ The in vitro data suggest that the bone-resorbing cells’ activity could be regulated by the degree of crystallinity of the bone mineral. These findings imply that changes in the properties of biogenic inorganic materials induce specific interactions with biomolecules, which in turn should define the cell’s behaviour. These results would support an interesting mechanism of cell regulation if confirmed in vivo.Nature Precedings 01/2009;