NDLI: Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank

Content Provider	PubMed Central
Author	Harmey, Dympna Hessle, Lovisa Narisawa, Sonoko Johnson, Kristen A. Robert, Terkeltaub Millán, José Luis
Copyright Year	2004
Abstract	Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PPi). Deletion of the TNAP gene ( Akp2 ) in mice results in hypophosphatasia characterized by elevated levels of PPi and poorly mineralized bones, which are rescued by deletion of nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) that generates PPi. Mice deficient in NPP1 ( Enpp1 −/−), or defective in the PPi channeling function of ANK ( ank/ank ), have decreased levels of extracellular PPi and are hypermineralized. Given the similarity in function between ANK and NPP1 we crossbred Akp2 −/− mice to ank/ank mice and found a partial normalization of the mineralization phenotypes and PPi levels. Examination of Enpp1 −/− and ank/ank mice revealed that Enpp1 −/− mice have a more severe hypermineralized phenotype than ank/ank mice and that NPP1 but not ANK localizes to matrix vesicles, suggesting that failure of ANK deficiency to correct hypomineralization in Akp2 −/− mice reflects the lack of ANK activity in the matrix vesicle compartment. We also found that the mineralization inhibitor osteopontin (OPN) was increased in Akp2 −/−, and decreased in ank/ank mice. PPi and OPN levels were normalized in [ Akp2 −/−; Enpp1 −/−] and [ Akp2 −/−; ank/ank ] mice, at both the mRNA level and in serum. Wild-type osteoblasts treated with PPi showed an increase in OPN, and a decrease in Enpp1 and Ank expression. Thus TNAP, NPP1, and ANK coordinately regulate PPi and OPN levels. The hypomineralization observed in Akp2 −/− mice arises from the combined inhibitory effects of PPi and OPN. In contrast, NPP1 or ANK deficiencies cause a decrease in the PPi and OPN pools that leads to hypermineralization.
Starting Page	1199
File Format	PDF
ISSN	15252191
e-ISSN	15252191
Journal	The American Journal of Pathology
Issue Number	4
Volume Number	164
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	2004-04-01
Access Restriction	Open
Rights Holder	American Society for Investigative Pathology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

The ank gene story

Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification

The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte

Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification

Override of the Osteoclast Defect in Osteopontin-Deficient Mice by Metastatic Tumor Growth in the Bone

The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte*

Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases

Osteopontin Inhibits Mineral Deposition and Promotes Regression of Ectopic Calcification

Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank

Similar Documents

Vanin-1 Pantetheinase Drives Increased Chondrogenic Potential of Mesenchymal Precursors in ank/ank Mice

The ank gene story

Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification

The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte

Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification

Override of the Osteoclast Defect in Osteopontin-Deficient Mice by Metastatic Tumor Growth in the Bone

The Inorganic Pyrophosphate Transporter ANK Preserves the Differentiated Phenotype of Articular Chondrocyte*

Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases

Osteopontin Inhibits Mineral Deposition and Promotes Regression of Ectopic Calcification

Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank