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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    • "Altogether, these findings suggest that the RANKL-- RANK-OPG system may partially mediate the effects of T3-treatment only in the femur and that this system may need an intact α 2C -AR signaling to work properly. We also evaluated the mRNA expression of bone turnover-related genes, such as osteocalcin (OC), which is expressed by mature osteoblasts [53], and tartrate-resistant acid phosphatase (TRAP), which is expressed by mature osteoclasts and is involved in bone resorption [54] . As expected, the supraphysiological T3 treatment increased mRNA expression of OC in the femur and vertebra of WT mice, which is a known effect of TH [13] . "
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    ABSTRACT: A series of studies have demonstrated that activation of the sympathetic nervous system (SNS) causes osteopenia via β2-adrenoceptor (β2-AR) signaling. However, in a recent study, we found an unexpected and generalized phenotype of high bone mass in female mice with chronic sympathetic hyperactivity, due to double gene inactivation of adrenoceptors that negatively regulate norepinephrine release, α2A-and α2C-AR (α2A/2C-AR-/-). These findings suggest that β2-AR is not the single adrenoceptor involved in bone turnover regulation and show that α2-AR signaling may also mediate the SNS actions in the skeleton. In addition, we found that α2A/2C-AR-/- animals are resistant to the thyrotoxicosis-induced osteopenia, suggesting that thyroid hormone (TH), when in supraphysiological levels, interacts with the SNS to control bone mass and structure, and that this interaction may also involve α2-AR signaling. In the present study, to further investigate these hypotheses and to discriminate the roles of α2-AR subtypes, we have evaluated the bone phenotype of mice with the single gene inactivation of α2C-AR subtype, which mRNA expression was previously shown to be down regulated by triiodothyronine (T3). A cohort of 30 day-old female α2CAR-/- mice and their wild-type (WT) controls were treated with a supraphysiological dose of T3 for 30 or 90 days, which induced a thyrotoxic state in both mouse lineages. The micro-computed tomographic (μCT) analysis showed that α2C-AR-/- mice present lower trabecular bone volume (BV/TV) and number (Tb.N), and increased trabecular separation (Tb.Sp) in the femur compared with WT mice; which was accompanied by decreased bone strength (determined by the three-point bending test) in the femur and tibia. The opposite was observed in the vertebra, where α2C-AR-/- mice show increased BV/TV, Tb.N and trabecular thickness (Tb.Th), and decreased Tb.Sp, compared with WT animals. In spite of the contrasting bone phenotypes of the femur and L5, thyrotoxicosis negatively regulated most of the micro architectural features of the trabecular bone in both skeletal sites of WT, but not of α2C-AR-/- mice. T3 treatment also decreased biomechanical properties (maximum load and ultimate load) in the femur and tibia of WT, but not of knockout mice. The mRNA expression of osteocalcin, a marker of mature osteoblasts, and tartrate-resistant acid phosphatase, which is expressed by osteoclasts and is involved in collagen degradation, was increased by T3 treatment only in WT, and not in α2C-AR-/- mice. Altogether, these findings suggest that α2C-AR subtype mediates the effects of the SNS in the bone in a skeletal site-dependent manner, and that thyrotoxicosis depends on α2C-AR signaling to promote bone loss, which sustains the hypothesis of a TH-SNS interaction to modulate bone remodeling and structure.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "NFATc1 functions as a master regulator of osteoclast differentiation and is activated by RANKLmediated dephosphorylation. Activated NFATc1 is transported to the nucleus where it induces the expression of genes involved in osteoclast differentiation, including tartrate-resistant acid phosphatase (TRAP; also known as ACP5), cathepsin K (CtsK), dendritic cell-specific transmembrane protein (DC-STAMP) and the d2 isoform of vacuolar ATPase V(0) domain (ATP6v0d2) (Hayman, 2008; Matsumoto et al., 2004; Yagi et al., 2007; Kim et al., 2008). TRAP-positive mononuclear precursors of osteoclasts fuse to form the mature multinuclear TRAP-positive osteoclast that is capable of bone resorption. "
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    ABSTRACT: Luman is a type II transmembrane transcription factor belonging to the OASIS family that localizes to the endoplasmic reticulum (ER) membrane under normal conditions. In response to ER stress, OASIS family members are subjected to regulated intramembrane proteolysis (RIP), following which the cleaved N-terminal fragments translocate to the nucleus. In this study, we show that treatment of bone marrow macrophages (BMMs) with cytokines, M-CSF and RANKL, causes a time-dependent increase in Luman expression and that Luman undergoes RIP and becomes activated during osteoclast differentiation. ShRNA-mediated knockdown of Luman in BMMs prevents the formation of multinucleated osteoclasts, concomitant with the suppression of DC-STAMP, a protein essential for cell'cell fusion in osteoclastogenesis. N-terminus of Luman facilitates promoter activities of DC-STAMP, resulting in up-regulation of DC-STAMP expression. Furthermore, Luman interacts with DC-STAMP, and controls its stability and localization. These results suggest that Luman regulates the multinucleation of osteoclasts by promoting cell fusion of mononuclear osteoclasts through DC-STAMP induction and intracellular distribution during osteoclastogenesis.
    Full-text · Article · Oct 2015 · Journal of Cell Science
    • "), which are related to the phagocytic nature of cells such as macrophages or osteoclasts[24,26]. Thus, further research should not only concentrate on the different macrophage polarization related to the physicochemical properties of biomaterials but also on different BMGC subtypes and correspondingly on their role in tissue regeneration in relation to the material-specific tissue reaction, Furthermore, the applications of marker molecules such as TRAP and its role in the " inflammatory " tissue reaction to biomaterials have to be examined in greater "
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    ABSTRACT: Biomaterial-associated multinucleated giant cells (BMGCs) have been found within the implantation beds of many different biomaterials. However, their exact differentiation and their involvement in the inflammatory and healing events of the foreign body response still remain mostly unclear. Silk fibroin (SF) scaffolds, which induces a tissue reaction involving both macrophages and BMGCs, was implanted in the subcutaneous connective tissue of four CD-1 mice for 15 days using an established subcutaneous implantation model. Analysis of macrophage polarization and BMGCs was performed by immunohistochemcial detection of pro- (cyclooxygenase-2 (COX-2), C-C chemokine receptor type 7 (CCR7), nuclear factor 'kappa-light-chain-enhancer' (NF-κB)) and anti- (heme oxygenase-1 (HO-1) and mannose receptor (MR, also known as CD206)). Furthermore, histochemical detection of tartrate-resistant acid phosphatase (TRAP) was conducted to test its predictive efficiency for the pro-inflammatory differentiation of cells. An established system for histomorphometrical analysis was used for counting of BMGCs expressing these molecules. The results show that BMGCs express both pro- and anti-inflammatory molecules within the implantation beds of SF scaffolds in comparable numbers, while only statistically significantly lower numbers of TRAP-positive BMGCs were measured in comparison to the BMGCs expressing the above-mentioned molecules. As these data substantiate the heterogeneity of BMGCs, the question arises to what extent BMGCs can „support“ the process of tissue regeneration. Furthermore, the data prompt the question to what extent TRAP-expression within a biomaterial implantation bed can be seen as a predictive marker for an inflammatory condition, as in this study no obvious correlation between TRAP-expression and other pro-inflammatory markers could be observed.
    No preview · Article · Sep 2015 · Journal of Biomedical Materials Research Part A
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