Search results
Items: 8
1.
Du G, Zhan H, Ding D, Wang S, Wei X, Wei F, Zhang J, Bilgen B, Reginato AM, Fleming BC, Deng J, Wei L.
Am J Sports Med. 2016 Mar;44(3):652-63. doi: 10.1177/0363546515621285.
- PMID:
- 26792705
2.
Millán JL.
Subcell Biochem. 2015;76:155-66. doi: 10.1007/978-94-017-7197-9_8. Review.
3.
Li Q, Price TP, Sundberg JP, Uitto J.
Cell Cycle. 2014;13(16):2609-15. doi: 10.4161/15384101.2014.943567.
4.
Sapir-Koren R, Livshits G.
Biofactors. 2014 Nov-Dec;40(6):555-68. doi: 10.1002/biof.1186. Review.
Abstract
Body phosphate homeostasis is regulated by a hormonal counter-balanced intestine-bone-kidney axis. The major systemic hormones involved in this axis are parathyroid hormone (PTH), 1,25-dihydroxyvitamin-D, and fibroblast growth factor-23 (FGF23). FGF23, produced almost exclusively by the osteocytes, is a phosphaturic hormone that plays a major role in regulation of the bone remodeling process. Remodeling composite components, bone mineralization and resorption cycles create a continuous influx-efflux loop of the inorganic phosphate (Pi) through the skeleton. This "bone Pi loop," which is formed, is controlled by local and systemic factors according to phosphate homeostasis demands. Although FGF23 systemic actions in the kidney, and for the production of PTH and 1,25-dihydroxyvitamin-D are well established, its direct involvement in bone metabolism is currently poorly understood. This review presents the latest available evidence suggesting two aspects of FGF23 bone local activity: (a) Regulation of FGF23 production by both local and systemic factors. The suggested local factors include extracellular levels of Pi and pyrophosphate (PPi), (the Pi/PPi ratio), and another osteocyte-derived protein, sclerostin. In addition, 1,25-dihydroxyvitamin-D, synthesized locally by bone cells, may contribute to regulation of FGF23 production. The systemic control is achieved via PTH and 1,25-dihydroxyvitamin-D endocrine functions. (b) FGF23 acts as a local agent, directly affecting bone mineralization. We support the assumption that under balanced physiological conditions, sclerostin, by para- autocrine signaling, upregulates FGF23 production by the osteocyte. FGF23, in turn, acts as a mineralization inhibitor, by stimulating the generation of the major mineralization antagonist-PPi.
5.
Bobryshev YV, Orekhov AN, Sobenin I, Chistiakov DA.
Curr Pharm Des. 2014;20(37):5821-8. Review.
Activation of bone-type tissue-nonspecific alkaline phosphatase
(TNAP) in vascular smooth muscle cells precedes vascular calcification.
By degrading PPi, TNAP plays a procalcific role changing the Pi/PPi ratio
toward mineralization. A pathologic role of bone-type TNAP and PHOSPHO1
make them to be attractive targets for cardiovascular therapy.
6.
Simão AM, Bolean M, Hoylaerts MF, Millán JL, Ciancaglini P.
Calcif Tissue Int. 2013 Sep;93(3):222-32. doi: 10.1007/s00223-013-9745-3.
TNAP and NPP1,
alone or combined, were reconstituted in dipalmitoylphosphatidylcholine
liposomes to mimic the microenvironment of MVs. The hydrolysis of ATP,
ADP, AMP, and PPi was studied at pH 8 and 9 and compared to the data
determined at pH 7.4.
While catalytic efficiencies in general were
higher at alkaline pH, PPi hydrolysis was maximal at pH 8 and indicated a
preferential utilization of PPi over ATP at pH 8 versus 9.
In addition,
all proteoliposomes induced mineral formation when incubated in a
synthetic cartilage lymph containing 1 mM ATP as substrate and amorphous
calcium phosphate(ACP) or calcium-phosphate-phosphatidylserine complexes as
nucleators.
Propagation of mineralization was significantly more
efficient at pH 7.5 and 8 than at pH 9.
Since a slight pH elevation from
7.4 to 8 promotes considerably more hydrolysis of ATP, ADP, and AMP
primarily by TNAP, this small pH change facilitates mineralization,
especially via upregulated PPi hydrolysis by both NPP1 and TNAP, further
elevating the Pi/PPi ratio, thus enhancing bone mineralization.Free PMC Article
7.
Mebarek S, Hamade E, Thouverey C, Bandorowicz-Pikula J, Pikula S, Magne D, Buchet R.
Curr Med Chem. 2011;18(14):2196-203. Review.
Abstract
In
this review we consider diseases associated with pathological
mineralization/ossification, namely, ankylosing spondylitis (AS),
osteoarthritis (OA), generalized artery calcification of infancy (GACI),
vascular calcification as well as chondrocalcinosis (CC) and pseudo
gout. Deciphering the key enzymes implicated in the calcification
process is an objective of prime importance and the ultimate goal is to
synthesize inhibitors of these enzymes in order to provide efficient
alternate therapeutic strategies that will slow down the pathologic
mineralization and complement the arsenal of anti-inflammatory drugs.
One of the difficulties in the definition of diseases associated with
pathologic mineralization/ossification lies in the controversial
relationship between the type of calcification and the nature of the
disease. Here, we propose to clarify this relationship by making a
distinction between diseases associated with hydroxyapatite (HA) and
calcium pyrophosphate dihydrate (CPPD) deposits.
AS, OA, GACI and vascular calcification are usually characterized by mineralization/ossification associated with HA deposits,
while CC and pseudo gout are mostly characterized by CPPD deposits.
Although both HA and CPPD deposits may occur concomitantly, as in chronic pyrophosphate arthritis or in OA with CPPD, they are formed as a result of two antagonistic processes indicating that treatment of distinct diseases can be only achieved by disease-specific drug therapies.
The hydrolysis of PPi, an inhibitor of HA formation, is mostly controlled by tissue non-specific alkaline phosphatase TNAP,
while PPi production in the extracellular medium is controlled by ANK, a PPi transporter, and/or NPP1 which generates PPi from nucleotide triphosphates.
Low PPi concentration may lead to a preferential deposition of HA while high PPi concentration will favor the formation of CPPD deposits. Thus, HA and CCPD deposition cannot occur concomitantly because they are determined by the Pi/PPi ratio which, in turn, depends on the relative activities of antagonistic enzymes, TNAP hydrolyzing PPi or ANK and NPP1 producing PPi.
TNAP inhibitors could prevent HA formation in AS, in late OA, in GACI, as well as in vascular calcifications, while ANK or NPP1 inhibitors could slow down CCPD deposition in CC and pseudo gout.
AS, OA, GACI and vascular calcification are usually characterized by mineralization/ossification associated with HA deposits,
while CC and pseudo gout are mostly characterized by CPPD deposits.
Although both HA and CPPD deposits may occur concomitantly, as in chronic pyrophosphate arthritis or in OA with CPPD, they are formed as a result of two antagonistic processes indicating that treatment of distinct diseases can be only achieved by disease-specific drug therapies.
The hydrolysis of PPi, an inhibitor of HA formation, is mostly controlled by tissue non-specific alkaline phosphatase TNAP,
while PPi production in the extracellular medium is controlled by ANK, a PPi transporter, and/or NPP1 which generates PPi from nucleotide triphosphates.
Low PPi concentration may lead to a preferential deposition of HA while high PPi concentration will favor the formation of CPPD deposits. Thus, HA and CCPD deposition cannot occur concomitantly because they are determined by the Pi/PPi ratio which, in turn, depends on the relative activities of antagonistic enzymes, TNAP hydrolyzing PPi or ANK and NPP1 producing PPi.
TNAP inhibitors could prevent HA formation in AS, in late OA, in GACI, as well as in vascular calcifications, while ANK or NPP1 inhibitors could slow down CCPD deposition in CC and pseudo gout.
8.
Cheng PT, Pritzker KP.
J Rheumatol. 1983 Oct;10(5):769-77.
Abstract
The
relationship between ambient ionic conditions that favor pyrophosphate
(PPi) versus phosphate (Pi) biomineralization is important to
understanding the pathogenesis of chondrocalcinosis. We studied aqueous
solutions at pH 7.4, 37 degrees C, [Na+] = 140 mM, [Mg+ +] = 0.5 mM,
[Ca+ +] = 1.0 or 1.5 mM over a range of pyrophosphate and phosphate
concentrations to determine the effect of different ambient
concentrations and ratios of Pi/PPi on calcium pyrophosphate dihydrate (CPPD) and calcium hydroxyapatite (HA) crystal formation.
We found that the Pi/PPi ratio is an extremely important determinant of the crystal product formed. At low [Pi], CPPD crystal formation is partially inhibited by Pi; at higher [Pi], calcium pyrophosphate, calcium phosphate and calcium pyrophosphate-phosphate complexes amorphous to x-ray diffraction are formed; whereas at still higher [Pi], HA crystal formation partially inhibited by PPi.
We conclude that CPPD forms when the ratio [Pi]/[PPi] less than 3 and HA forms when [Pi]/[PPi] greater than 100.
We found that the Pi/PPi ratio is an extremely important determinant of the crystal product formed. At low [Pi], CPPD crystal formation is partially inhibited by Pi; at higher [Pi], calcium pyrophosphate, calcium phosphate and calcium pyrophosphate-phosphate complexes amorphous to x-ray diffraction are formed; whereas at still higher [Pi], HA crystal formation partially inhibited by PPi.
We conclude that CPPD forms when the ratio [Pi]/[PPi] less than 3 and HA forms when [Pi]/[PPi] greater than 100.
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