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Tartrate-resistant acid phosphatase

About: Tartrate-resistant acid phosphatase is a research topic. Over the lifetime, 1115 publications have been published within this topic receiving 45937 citations. The topic is also known as: HPAP & SPENCDI.


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Journal Article
TL;DR: This review summarizes the scientific knowledge on the role of TRACP in osteoclastic bone resorption, the mechanism ofTRACP 5b generation in osteoblasts and its secretion into the blood circulation, the methodology of measuring TRACP 5a, diagnostic evidence for the use of TRACP 5b as a resorptive marker, and characteristics of TR ACP 5a compared to other commonly used bone turnover markers.
Abstract: Tartrate-resistant acid phosphatase (TRACP) is an enzyme that is expressed in high amounts by bone resorbing osteoclasts, inflammatory macrophages and dendritic cells. Two forms of TRACP circulate in human blood, TRACP 5a derived from macrophages and dendritic cells, and TRACP 5b derived from osteoclasts. Recent data have demonstrated the utility of TRACP 5b as a marker of osteoclast number and bone resorption, and serum TRACP 5a as a marker of inflammatory conditions. This review summarizes the scientific knowledge on the role of TRACP in osteoclastic bone resorption, the mechanism of TRACP 5b generation in osteoclasts and its secretion into the blood circulation, the methodology of measuring TRACP 5b, diagnostic evidence for the use of TRACP 5b as a resorption marker, and characteristics of TRACP 5b compared to other commonly used bone turnover markers.

225 citations

Journal ArticleDOI
TL;DR: Findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type Iinterferon in the genesis of autoimmunity.
Abstract: We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjogren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

215 citations

Journal ArticleDOI
TL;DR: It is proposed that this new role of MMPs is a major component of the mechanism that determines where and when the osteoclasts will attack the bone.
Abstract: A key event in bone resorption is the recruitment of osteoclasts to future resorption sites, We follow here the migration of preosteoclasts from the periosteum to the developing marrow cavity of fetal mouse metatarsals in culture, and investigate the role of proteinases and demineralization in this migration, Our approach consisted in testing inhibitors of proteinases and demineralization on the migration kinetics, Migration was monitored by histomorphometry and the (pre)osteoclasts were identified by their tartrate resistant acid phosphatase (TRAP) activity, At the time of explantation, TRAP+ cells (all mononucleated) are detected only in the periosteum, and the core of the diaphysis (future marrow cavity) consists of calcified cartilage, Upon culture, TRAP+ cells (differentiating progressively into multinucleated osteoclasts) migrate through a seam of osteoid and a very thin and discontinuous layer of mineral, invade the calcified cartilage and transform it into a 'marrow' cavity; despite the passage of maturing osteoclasts, the osteoid develops into a bone collar, The migration of TRAP+ cells is completely prevented by matrix metalloproteinase (MMP) inhibitors, but not by a cysteine proteinase inhibitor, an inhibitor of carbonic anhydrase, or a bisphosphonate, The latter three drugs inhibit, however, the resorptive activity of mature osteoclasts at least as efficiently as do the MMP inhibitors, as assessed in cultures of calvariae and radii, Furthermore, in situ hybridizations reveal the expression of 2 MMPs, gelatinase B (MMP-9 or 92 kDa type IV collagenase) in (pre)osteoclasts, and interstitial collagenase (MMP-13) in hypertrophic chondrocytes, Tt is concluded that only MMPs appear obligatory for the migration of (pre)osteoclasts, and that this role is distinct from the one MMPs may play in the subosteoclastic resorption compartment, We propose that this new role of MMPs is a major component of the mechanism that determines where and when the osteoclasts will attack the bone.

215 citations

Journal ArticleDOI
01 Nov 2000-Bone
TL;DR: The view that TRAP, like several other hydrolases, is synthesized as a relatively inactive proen enzyme, and cleavage is the physiological mechanism of proenzyme activation in osteoclasts is put forth.

210 citations

Journal ArticleDOI
TL;DR: It is suggested that histochemical demonstration of TR-AP versus TS-AP on GMA-embedded bone sections by means of a pre-incubation method can be used as an identification marker of (pre)osteoclasts.
Abstract: Fixed, undecalcified mouse long bones were embedded in glycol methacrylate (GMA), sectioned, and incubated for acid phosphatase in the presence or absence of tartrate, to investigate the feasibility of tartrate-resistant acid phosphatase as a histochemical marker for osteoclast identification. Naphthol AS-BI phosphate was used as the substrate and hexazonium pararosanaline as coupler. Cytocentrifuge preparations of mouse, rat, and quail bone marrow or frozen and GMA sections of mouse splenic tissue were used as controls to specify acid phosphatase activity. After adequate fixation, acid phosphatase activity sensitive to tartrate inhibition (TS-AP) was demonstrated in macrophages from spleen, bone marrow, and loose connective tissue surrounding bone rudiments. Acid phosphatase activity resistant to tartrate inhibition (TR-AP), was detected in multi-nuclear osteoclasts and in some mononuclear cells from bone marrow and periosteum. In cytocentrifuge preparations and frozen sections of mouse spleen, TR-AP was demonstrated after simultaneous incubation with substrate and tartrate. In GMA sections, however, TR-AP could only be demonstrated after pre-incubation with tartrate before application of substrate. We suggest that histochemical demonstration of TR-AP versus TS-AP on GMA-embedded bone sections by means of a pre-incubation method can be used as an identification marker of (pre)osteoclasts. Plastic embedding is recommended for its excellent preservation of morphology and enzyme activity.

202 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20239
202238
202126
202025
201913
201821