Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Limb bud mesenchymal cells from mouse embryos grown at high density at the medium/air interphase undergo chondrogenesis and form numerous nodules of mature cartilage. Addition of beta-glycerophosphate (5 mM) induced endochondral mineralization within these nodules. Ca2+ accumulation, matrix formation and alkaline phosphatase activity were recorded for each culture. Treatment with the L-type channel-specific blockers nifedipine and verapamil during the entire culture period caused an inhibition of mineralization. Sequential treatment reduced mineralization only when added during the early part of the culture period in the course of chondrogenesis. In all cases, matrix formation, estimated by alcian blue binding, was concomitantly diminished. Lanthanum acetate, which blocks Ca2+ channels non-specifically, also reduced Ca2+ accumulation in the cultures when added continuously. After sequential treatment, Ca2+ content was only diminished when the cultures were treated in the last part of the culture period during mineralization. Matrix formation was not altered by lanthanum acetate, but alkaline phosphatase was decreased. These results show that chondrogenic differentiation is under control of L-type Ca2+ channels, whereas matrix calcification depends on intracellular Ca2+ accumulation mediated by lanthanum-sensitive Ca2+ channels. This points to the importance of intracellular Ca2+ accumulation in the process of endochondral mineralization.
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PMID:Inhibition of chondrogenesis and endochondral mineralization in vitro by different calcium channel blockers. 800 98

Lanthanum, a rare earth element, has been used to decrease serum phosphorus level in patients with chronic renal disease and hyperphosphatemia. We aimed to observe the effect and mechanism of two doses of lanthanum acetate (375 and 750 mg/kg/day) on vascular calcification induced by vitamin D3 plus nicotine treatment in rats for 4 weeks. As compared with control rats, rats with calcification showed widespread calcified nodules and irregular elastic fibers in calcified aorta on von Kossa calcium staining and increased aortic calcium and phosphorus contents, alkaline phosphatase (ALP) activity and bone-related protein expressions for osteopontin (OPN) and type III sodium dependent phosphate cotransporter Pit-1 (Pit-1). After treatment with either dose of lanthanum acetate, the calcified nodules and degree of irregular elastic fibers decreased in aortas. Lanthanum acetate at 750 mg/kg/day was more effective than 375 mg/kg/day in lessening vascular calcification by significantly reducing plasma phosphorus level, calcium x phosphorus product and ALP activity, by 30.3%, 28.6%, and 68.6%, respectively; reducing aortic phosphorus and calcium contents and ALP activity, by 48%, 53.1%, and 63.5% (all P < 0.01), respectively; reducing aortic mRNA level of OPN and Pit-1, by 55.8% (P < 0.01) and 38.8% (P < 0.05) and protein level of OPN and Pit-1, by 37.2% and 27.2% (both P < 0.01), respectively; and increasing carboxylated matrix Gla-protein (MGP) protein expression by 33.7% (P < 0.05), as compared with rats treated with vitamin D3 and nicotine alone. Lanthanum acetate could effectively inhibit the pathogenesis of vascular calcification.
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PMID:Lanthanum acetate inhibits vascular calcification induced by vitamin D3 plus nicotine in rats. 1954 57