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.

Tartrate-Resistant Acid Phosphatase as an Immunohistochemical Marker for Inflammatory Macrophages

Abstract: Human serum contains 2 isoforms of type-5 tartrate-resistant acid phosphatase (TRACP): 5a and 5b. TRACP-5b is osteoclastic. Our goal was to determine if serum TRACP-5a could originate from inflammatory macrophages (MPhi). We stained 246 paraffin-embedded tissue samples for TRACP using monoclonal antibody 9C5 (mab9C5) to isoforms 5a and 5b and a novel mab220 specific to isoform 5a. CD68 and lysozyme were also stained. MPhi of chronic and granulomatous inflammation and in tissues that undergo strong antigenic stimulation were strongly positive for TRACP, more so with mab220 than with mab9C5. Noninflammatory MPhi in lymph node sinuses or germinal centers and red pulp MPhi of spleen were weak or negative for TRACP. Marginal zone lymphocytes and sebaceous glands of skin were weakly positive for TRACP. Tissue mast cells displayed strong TRACP staining. Neuroendocrine cells of gastrointestinal tissues were strongly immunoreactive with mab9C5 but negative with mab220. Restricted expression of TRACP primarily in inflammatory MPhi supports our hypothesis that circulating TRACP-5a could be a biomarker of chronic inflammatory disease activity.

Norisoboldine Suppresses Osteoclast Differentiation through Preventing the Accumulation of TRAF6-TAK1 Complexes and Activation of MAPKs/NF-κB/c-Fos/NFATc1 Pathways

Abstract: Norisoboldine (NOR) is the main alkaloid constituent in the dry root of Lindera aggregata (Sims) Kosterm. (L. strychnifolia Vill.). As reported previously, orally administered NOR displayed a robust inhibition of joint bone destruction present in both mouse collagen-induced arthritis and rat adjuvant-induced arthritis with lower efficacious doses than that required for ameliorating systemic inflammation. This attracted us to assess the effects of NOR on differentiation and function of osteoclasts, primary effector cells for inflammatory bone destruction, to get insight into its anti-rheumatoid arthritis mechanisms. Both RAW264.7 cells and mouse bone marrow-derived macrophages (BMMs) were stimulated with RANKL (100 ng/mL) to establish osteoclast differentiation models. ELISA, RT-PCR, gelatin zymography, western blotting, immunoprecipitation and EMSA were used to reveal related signalling pathways. NOR (10 and 30 µM), without significant cytotoxicity, showed significant reduction of the number of osteoclasts and the resorption pit areas, and it targeted osteoclast differentiation at the early stage. In conjunction with the anti-resorption effect of NOR, mRNA levels of cathepsin K and MMP-9 were decreased, and the activity of MMP-9 was attenuated. Furthermore, our mechanistic studies indicated that NOR obviously suppressed the ubiquitination of TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of ERK and p38 MAPK, and reduced the nuclear translocation of NF-κB-p65 and DNA-binding activity of NF-κB. However, NOR had little effect on expressions of TRAF6 or the phosphorylation and degradation of IκBα. Moreover, NOR markedly inhibited expressions of transcription factor NFATc1, but not c-Fos. Intriguingly, the subsequent nuclear translocations of c-Fos and NFATc1 were substantially down-regulated. Hence, we demonstrated for the first time that preventing the differentiation and function of osteoclasts at the early stage was an important anti-bone destruction mechanism of NOR, which might be attributed to inhibition of ubiquitination of TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of MAPKs/NF-κB/c-Fos/NFATc1 pathways.

Differential effects of glucocorticoid on recruitment and activity of osteoclasts induced by normal and osteocalcin-deficient bone implanted in rats.

Abstract: Prolonged glucocorticoid excess is associated with bone loss. Among the contributory factors are glucocorticoids' suppression of bone formation and stimulation of bone resorption. In this study, the effects of glucocorticoids on bone resorption were evaluated in a rodent model. Subcutaneous implants of devitalized mineralized bone particles (BPs) elicit the recruitment of progenitor cells and their differentiation to osteoclasts which resorb the BPs. The effects of glucocorticoids on both the recruitment and the activity of cells induced by normal BPs were distinguished based upon when treatment was initiated. When treatment with hydrocortisone or dexamethasone was initiated at the time of BP implantation, the recruitment of bone-resorbing cells was impaired and a subsequent decrease in BP resorption was found. On the other hand, when treatment was initiated on day 7, glucocorticoids increased osteoclastic resorption and tartrate-resistant acid phosphatase activity. We also tested hydrocortisone's effect ...

Differentiation of HL-60 cells into cells with the osteoclast phenotype.

Abstract: The osteoclast is the unique multinucleated cell that is responsible for bone degradation in both physiological and pathological circumstances. However, knowledge of the lineage of this inaccessible cell, the nature of its precursors, and the regulation of its formation and activation is limited and controversial. Here we show that the human promyelocytic cell line HL-60 has the potential, under the appropriate culture conditions, to differentiate into cells that have morphological and functional characteristics of osteoclasts, including multinucleation, presence of tartrate-resistant acid phosphatase activity, cross-reactivity with monoclonal antibodies that preferentially recognize osteoclasts, and capacity to resorb bone and respond to calcitonin. The multinucleated cells also contain high affinity receptors to calcitonin, in contrast to wild-type undifferentiated HL-60 cells. These data suggest that osteoclasts share a common precursor with hematopoietic cells. These undifferentiated and differentiated HL-60 cells should provide a unique model for study of the cell biology of human osteoclast differentiation, allowing molecular biological and biochemical studies heretofore not possible.