ANKH - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

ANKH

The Experts below are selected from a list of 846 Experts worldwide ranked by ideXlab platform

Florence W L Tsui – 1st expert on this subject based on the ideXlab platform

  • Genetics and Mechanisms of Crystal Deposition in Calcium Pyrophosphate Deposition Disease
    Current Rheumatology Reports, 2012
    Co-Authors: Florence W L Tsui

    Abstract:

    Calcium pyrophosphate deposition (CPPD) disease (common in older adults) can be asymptomatic, associated with osteoarthritis, or can present as acute/chronic inflammatory arthritis. Due to the phenotypic complexity of CPPD, the European League Against Rheumatism (EULAR) recently made recommendations on terminology, diagnosis, and management based on available research evidence and expert consensus. There are no disease-modifying treatments for CPPD disease, and therapy remains nonspecific with the use of anti-inflammatory and analgesic drugs. For years, it has been known that inorganic phosphate and pyrophosphate regulate the formation of CPP or hydroxyapatite crystals. The discovery of ANKH (human homologue of progressive ankylosis ) mutations in familial CPPD disease confirmed the importance of phosphate/pyrophosphate homeostasis in CPPD, with ANKH being a regulator of inorganic pyrophosphate transport. Despite progress in our understanding of the function of ANKH, much remains to be investigated. This review summarizes the genetic basis of this disease and focuses on the challenges of research in this area.

  • the cppdd associated ANKH m48t mutation interrupts the interaction of ANKH with the sodium phosphate cotransporter pit 1
    The Journal of Rheumatology, 2009
    Co-Authors: John L Wang, Frank Beier, Hing Wo Tsui, Florence W L Tsui

    Abstract:

    Objective. Numerous dominant human homolog of progressive ankylosis ( ANKH ) mutations have been identified in familial calcium pyrophosphate dihydrate crystal deposition disease (CPPDD). Due to the dominant nature of these mutations, we investigated whether ANKH interacts with other proteins; and if so, whether any CPPDD-associated ANKH mutation might disrupt such protein interactions.

    Methods. Stable ATDC5 ANKH wt- and ANKH M48T- transfectants were generated. Lysates from these transfectants were used to identify candidate protein interaction with ANKH by coimmunoprecipitation followed by Western blot analysis. The effect of high phosphate on the expression of genes involved in modulating Pi (inorganic phosphate)/PPi (inorganic pyrophosphate) homeostasis in these transfectants was assessed.

    Results. We showed that ANKH protein associates with the sodium/phosphate cotransporter PiT-1, and that ANKH M48T mutant protein failed to interact with PiT-1. We also showed that upon high phosphate treatment, the normally coordinated upregulation of endogenous Ank and PiT1 transcript expression was disrupted in ANKH M48T transfectants.

    Conclusion Our results suggested that there is a coordinated interrelationship between 2 key participants of Pi and PPi metabolism, ANKH and PiT-1.

  • The CPPDD-Associated ANKH M48T Mutation Interrupts the Interaction of ANKH with the Sodium/Phosphate Cotransporter PiT-1
    The Journal of Rheumatology, 2009
    Co-Authors: John L Wang, Frank Beier, Hing Wo Tsui, Florence W L Tsui

    Abstract:

    Objective. Numerous dominant human homolog of progressive ankylosis ( ANKH ) mutations have been identified in familial calcium pyrophosphate dihydrate crystal deposition disease (CPPDD). Due to the dominant nature of these mutations, we investigated whether ANKH interacts with other proteins; and if so, whether any CPPDD-associated ANKH mutation might disrupt such protein interactions.

    Methods. Stable ATDC5 ANKH wt- and ANKH M48T- transfectants were generated. Lysates from these transfectants were used to identify candidate protein interaction with ANKH by coimmunoprecipitation followed by Western blot analysis. The effect of high phosphate on the expression of genes involved in modulating Pi (inorganic phosphate)/PPi (inorganic pyrophosphate) homeostasis in these transfectants was assessed.

    Results. We showed that ANKH protein associates with the sodium/phosphate cotransporter PiT-1, and that ANKH M48T mutant protein failed to interact with PiT-1. We also showed that upon high phosphate treatment, the normally coordinated upregulation of endogenous Ank and PiT1 transcript expression was disrupted in ANKH M48T transfectants.

    Conclusion Our results suggested that there is a coordinated interrelationship between 2 key participants of Pi and PPi metabolism, ANKH and PiT-1.

Charlene J. Williams – 2nd expert on this subject based on the ideXlab platform

  • Mutations in osteoprotegerin account for the CCAL1 locus in calcium pyrophosphate deposition disease
    Osteoarthritis and Cartilage, 2018
    Co-Authors: Charlene J. Williams, U. Qazi, M. Bernstein, A. Charniak, Claudia M. Gohr, Elizabeth Mitton-fitzgerald, A. Ortiz, L. Cardinal, A.t. Kaell, Ann K. Rosenthal

    Abstract:

    Summary Objective Mutations on chromosomes 5p (CCAL2) and 8q (CCAL1) have been linked to familial forms of calcium pyrophosphate deposition disease (CPDD). Mutations in the ANKH gene account for CCAL2, but the identity of CCAL1 has been elusive. Recently, a single Dutch kindred with a mutation in the Tumor Necrosis Factor Receptor Super Family member 11B (TNFRSF11B) gene coding for osteoprotegerin (OPG) was described as a gain-of-function mutation. Affected family members had premature generalized osteoarthritis (PGOA) and CPDD. As the TNFRSF11B gene is on 8q, we sought additional evidence that TNFRSF11B was CCAL1, and investigated potential disease mechanisms. Design DNA from two novel PGOA/CPDD families was screened for sequence variants in the TNFRSF11B gene. Mutations were verified by genotype analysis of affected and unaffected family members. We also investigated effects of normal and mutant OPG on regulators of CPP crystal formation in porcine cartilage. Results The identical TNFRSF11B mutation described in the Dutch family was present in two novel PGOA/CPDD families. ANKH was normal in affected patient fibroblasts. Exogenous OPG did not alter ANKH mRNA or protein levels, affect translocation of ANKH to the membrane, nor increase [pyrophosphate (PPi)] or other key regulators of CPDD. Conclusion We have firmly established the identity of CCAL1 as TNFRSF11B (OPG). Our findings suggest that this mutation produces disease in an ANKH-independent manner via novel mechanisms not primarily targeting cartilage. This work rationalizes further investigation of OPG pathway components as potential druggable targets for CPDD.

  • Genetics of chondrocalcinosis
    Osteoarthritis and Cartilage, 2005
    Co-Authors: Raihana Zaka, Charlene J. Williams

    Abstract:

    Summary Rapid developments in genetic analysis have enabled the dissection of a variety of arthropathies that are inherited in a Mendelian manner. These disorders include calcium crystal arthropathies such as calcium pyrophosphate dihydrate deposition (CPPD) disease and hydroxyapatite deposition disease. In CPPD disease, mutations in a recently discovered gene, ANKH, have been demonstrated in five affected families and may also be associated with the idiopathic deposition of calcium pyrophosphate dihydrate crystals. The product of ANKH appears to be involved in cellular transport of inorganic pyrophosphate (PPi) and mutations in ANKH have been shown to have a significant impact on the regulation of intra- and extracellular levels of PPi. In families with hydroxyapatite deposition disease, no gene locus has yet been linked to the disorder.

  • mutations in the amino terminus of ANKH in two us families with calcium pyrophosphate dihydrate crystal deposition disease
    Arthritis & Rheumatism, 2003
    Co-Authors: Charlene J. Williams, Adrian Pendleton, Gina Bonavita, Antonio J Reginato, Anne E Hughes, Shelly Peariso, Michael Doherty, Daniel J. Mccarty, Lawrence M. Ryan

    Abstract:

    Objective

    To analyze ANKH in families with calcium pyrophosphate dihydrate crystal deposition disease (CPPD) for disease-causing mutations.

    Methods

    Two US families (one of British ancestry and the other of German/Swiss ancestry) with autosomal-dominant CPPD, whose disease phenotypes were found to be linked to chromosome 5p15.1 (locus symbol CCAL2), were screened by direct sequencing for mutations in ANKH, a gene in the CCAL2 candidate interval that has been shown to harbor mutations in other families with CPPD. Observed sequence variants were confirmed by antisense sequencing, and expression of the mutant allele was verified by reverse transcriptase–polymerase chain reaction amplification of messenger RNA followed by direct sequencing.

    Results

    The two US families displayed the same mutation at position 5 of the ANKH gene product (P5T). All affected members were heterozygous for the P-to-T variant, and the mutation was not seen in 204 control alleles. The two families displayed distinct disease haplotypes, suggesting that they were unrelated to each other.

    Conclusion

    These observations represent the fourth and fifth families with heritable CPPD whose disease phenotypes are linked to the CCAL2 locus and who have missense mutations in the amino terminus of ANKH. This same position (P5) was the site of a missense mutation in an Argentinean family of northern Italian ancestry; however, the sequence variant in that family generated a P5L mutation. The distinct disease haplotypes among the 3 families with P5 mutations suggest that the mutations arose independently and that the evolutionarily conserved P5 position of ANKH may represent a hot spot for mutation in families with autosomal-dominant CPPD.

Hing Wo Tsui – 3rd expert on this subject based on the ideXlab platform

  • the cppdd associated ANKH m48t mutation interrupts the interaction of ANKH with the sodium phosphate cotransporter pit 1
    The Journal of Rheumatology, 2009
    Co-Authors: John L Wang, Frank Beier, Hing Wo Tsui, Florence W L Tsui

    Abstract:

    Objective. Numerous dominant human homolog of progressive ankylosis ( ANKH ) mutations have been identified in familial calcium pyrophosphate dihydrate crystal deposition disease (CPPDD). Due to the dominant nature of these mutations, we investigated whether ANKH interacts with other proteins; and if so, whether any CPPDD-associated ANKH mutation might disrupt such protein interactions.

    Methods. Stable ATDC5 ANKH wt- and ANKH M48T- transfectants were generated. Lysates from these transfectants were used to identify candidate protein interaction with ANKH by coimmunoprecipitation followed by Western blot analysis. The effect of high phosphate on the expression of genes involved in modulating Pi (inorganic phosphate)/PPi (inorganic pyrophosphate) homeostasis in these transfectants was assessed.

    Results. We showed that ANKH protein associates with the sodium/phosphate cotransporter PiT-1, and that ANKH M48T mutant protein failed to interact with PiT-1. We also showed that upon high phosphate treatment, the normally coordinated upregulation of endogenous Ank and PiT1 transcript expression was disrupted in ANKH M48T transfectants.

    Conclusion Our results suggested that there is a coordinated interrelationship between 2 key participants of Pi and PPi metabolism, ANKH and PiT-1.

  • The CPPDD-Associated ANKH M48T Mutation Interrupts the Interaction of ANKH with the Sodium/Phosphate Cotransporter PiT-1
    The Journal of Rheumatology, 2009
    Co-Authors: John L Wang, Frank Beier, Hing Wo Tsui, Florence W L Tsui

    Abstract:

    Objective. Numerous dominant human homolog of progressive ankylosis ( ANKH ) mutations have been identified in familial calcium pyrophosphate dihydrate crystal deposition disease (CPPDD). Due to the dominant nature of these mutations, we investigated whether ANKH interacts with other proteins; and if so, whether any CPPDD-associated ANKH mutation might disrupt such protein interactions.

    Methods. Stable ATDC5 ANKH wt- and ANKH M48T- transfectants were generated. Lysates from these transfectants were used to identify candidate protein interaction with ANKH by coimmunoprecipitation followed by Western blot analysis. The effect of high phosphate on the expression of genes involved in modulating Pi (inorganic phosphate)/PPi (inorganic pyrophosphate) homeostasis in these transfectants was assessed.

    Results. We showed that ANKH protein associates with the sodium/phosphate cotransporter PiT-1, and that ANKH M48T mutant protein failed to interact with PiT-1. We also showed that upon high phosphate treatment, the normally coordinated upregulation of endogenous Ank and PiT1 transcript expression was disrupted in ANKH M48T transfectants.

    Conclusion Our results suggested that there is a coordinated interrelationship between 2 key participants of Pi and PPi metabolism, ANKH and PiT-1.

  • the ANKH δe490mutation in calcium pyrophosphate dihydrate crystal deposition disease cppdd affects tissue non specific alkaline phosphatase tnap activities
    The Open Rheumatology Journal, 2008
    Co-Authors: John L Wang, Frank Beier, Robert D. Inman, Hing Wo Tsui, Kenneth P.h. Pritzker, Florence W L Tsui

    Abstract:

    ANKH (human homolog of progressive ankylosis) regulates inorganic pyrophosphate (PPi) transport. Dominant ANKH mutations were detected in at least five multiplex families with calcium pyrophosphate dihydrate crystal deposition disease (CPPPD). The objective of this study is to assess the functional consequences of one CPPDD-associated ANKH mutation (ΔE490) in chondrogenic ATDC5 cells. Stable ATDC5 transfectants bearing myc-tagged constructs of wild-type ANKH, mutant ANKH (ΔE490) and neo controls were generated. Upon ITS (insulin, transferrin and selenium) induction, expression of chondrocyte markers including alkaline phosphatase activity in the various transfectants was assessed. The ANKH ΔE490- transfectants had low alkaline phosphatase activities throughout ITS treatment due to lower TNAP protein expression and the presence of intracellular low-molecular-weight inhibitors. Our results suggest that the interplay of ANKH and TNAP activities is tightly regulated.