Osteoclasts acid phosphatase

Kim MS, Day CJ, Selinger Cl, Magno CL, Stephens SR, Morrison NA. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATcl, and calcitonin receptor-positive but require receptor activator of NFkap-paB ligand for bone resorption. J Biol Chem 2006 281(2) 1274-1285. 

Moreover, as expected disruption of genes coding for enzymes critical to the function of osteoclast such as tartrate-resistant acid phosphatase (Hayman et al., 1996) and cathepsin K (Gowen et al., 1999) also produced osteopetrosis. This complements earlier discussed spontaneous osteopetrotic phenotypes produced by interception of pathways generating either protons or chloride necessary for mineral dissolution. 

Bone contains two distinct enzymes, acid and alkaline phosphatases, which are associated with osteoclasts and osteoblasts, respectively (118). Further study of acid phosphatase and bone should be rewarding. Many... 

Halleen, J.M., Raisanen, S., Salo, J.J., Reddy, S.V., Roodman, G.D., Hentunen, T.A., Lehenkari, P.P., Kaija, H., Vihko, P., and Vaananen, H.K. 1999. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase. J. Biol. Chem. 274, 22907-22910. 

Activity of the cells participating in bone remodeling. Usually it is the activity of the specific enzymes characteristic for the osteoblasts (especially alkaline phosphatase and its bone isoenzyme) or the osteoclasts, respectively (acid phosphatase or its bone isoenzyme)... 

HI. Halleen, J. M., Karp, M., Viloma, S., Laaksonen, P., Heilman, J., et al., Two-site immunoassays for osteoclastic tartrate-resistant acid phosphatase based on characterization of six monoclonal antibodies. J. Bone Miner. Res. 14,464-469 (1999). 

Purple acid phosphatases. Diiron-tyrosinate proteins with acid phosphatase activity occur in mammals, plants, and bacteria. Most are basic glycoproteins with an intense 510- to 550-nm light absorption band. Well-studied members come from beef spleen, from the uterine fluid of pregnant sows (uteroferrin), and from human macrophages and osteoclasts. " " One of the two iron atoms is usually in the Fe(III) oxidation state, but the second can be reduced to Fe(II) by mild reductants such as ascorbate. This half-reduced form is enzymatically active and has a pink color and a characteristic EPR signal. Treatment with oxidants such as H2O2 or hexacyannoferrate (III)... 

Bone enzymes are direct products of active osteoblasts (bone ALP) and osteoclasts (tartrate-resistant acid phosphatase). 

Moss DW. Changes in enzyme expression related to differentiation and regulatory factors the acid phosphatase of osteoclasts and other macrophages. Clin Chim Acta 1992 209 131-8. 

During bone resorption, osteoclasts produce and secrete an acid phosphatase. The activity of this TRAP has been measured using a number of methods. Unfortunately, most methods failed to distinguish between the osteclastic TRAP (isoform 5b) and other TRAPs (isoform 5a) found in plasma." In addition, instability of the enzyme and association of the enzyme with a2-macroglulin have complicated... 

Kraenzlin ME, Lau KHW, Liang L, Freeman TK, Singer FR, Stepan J, et al. Development of an immunoassay for serum osteoclastic tartrate resistant acid phosphatase. J Clin Endocrinol Metab 1990 71 442-51. 

Bone specific acid phosphatase A lysosomal enzyme of osteoclasts Urine Markers All of these are collagen breakdown products... 

The nature of the metal-ions in the active site also varies between species. Whereas the purple acid phosphatase isolated from red kidney beans (rkbPAP) contains Fe and Zn", the tartrate-resistant acid phosphatase isolated from rat osteoclasts (TRAcP) contains two iron atoms in different oxidation states, an stabilized Fe ion and a redox-active Fe ion. In this way, the ability of the ferrous ion to act as an electron donor confers to the enzyme an alternative function as generator of reactive oxygen species (ROS) [20, 21]. The enzyme may appear in an inactive purple form when the redox-active iron is oxidized to the ferric state, or it can be in an active pink form where the redox-active iron is reduced to the ferrous state [22]. In particular, the tartrate-resistant acid phosphatase isolated from osteoclasts is synthetized as a precursor which is activated by cysteine proteinases resulting in an active two subunit enzyme [23]. 

In vitro studies have shown that TRAcP 5b isoform remains intracellularly in macrophages and dendritic cells which only secrete the TRAcP 5a isoform [25]. Therefore, for clinical determinations it is assumed that the tartrate-resistant acid phosphatase activity associated with bone resorbing osteoclasts derives only from the TRAcP 5 b isoform. 

HaUeen JM, Raisanen S, Salo JJ et al (1999) Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phosphatase. J Biol Chem 274 22907-22910... 

To clarify the mechanism of action of these diterpenoids on bone resorption, their effect on osteoclast-like cell formation was tested according to the method reported by Takahashi et al.[34]. As a result, both compounds dose-dependently inhibited PTH-induced tartrate resistant acid phosphatase-positive MNC formation. Especially, SDC showed complete inhbition at concentration over 0.1 pM. Next, the effect of SDB and SDC on resorbing activity of osteoclasts (pit forming activity of osteoclast-like cells) was assayed according to the method of Tamura et al. [35]. As indicated in Table 8, both compounds inhibited the pit-formation when osteoclasts obtained by the co-culture were placed on dentine slice in the presence of these compounds. Therefore, the inhibitory effect of... 

Filgueira L (2004) Fluorescence-based staining for tartrate-resistant acidic phosphatase (TRAP) in osteoclasts combined with other fluorescent dyes and protocols. J Histochem Cytochem 52 411-414... 

Substitution of oxygen to carbon makes them resistant to rapid hydrolysis by phosphatase, an enzyme with widespread distribution in the body. More importantly, the replacement of the oxygen atom between the two phosphonic acid moieties of pyrophosphate by a carbon atom opened up the possibility of attaching side chains. The nature of the groups attached to the central carbon atom is the key to the optimization of bisphosphonates as potent inhibitors of osteoclastic bone resorption. The action of the bisphosphonates on calcium salts is similar to the action of pyrophosphates. They exhibit the following actions ... 

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