Searchable abstracts of presentations at key conferences on calcified tissues

ba0006is05 | (1) (1) | ICCBH2017

Skeletal mineralization – enzymes and animal models

Millan Jose Luis

Increased understanding of the biochemical pathways leading to MV-mediated initiation of skeletal, dental and vascular calcification has been attained through the extensive use of single and double knockout mouse models as well as via overexpression of genes by transgenesis. Our current integrated model of these pathways is compatible with the following sequence of events: MVs initiate mineral deposition by accumulation of Pi generated intravesicularly by the action...

ba0006is05biog | (1) (1) | ICCBH2017

Skeletal mineralization – enzymes and animal models

Millan Jose Luis

Biographical DetailsJosé Luis MillánProfessor José Luis Millán received his early training in clinical chemistry and biochemistry at the University of Buenos Aires, Argentina, and his PhD in Physiological Chemistry at the University of Umeå, Sweden, in 1983. Professor Millán is currently based at the Children’s Hea...

ba0001oc6.1 | Mineralisation and energy metabolism | ECTS2013

Npp1 is a key regulator of skeletal and soft tissue mineralisation

Hajjawi Mark , MacRae Vicky , Huesa Carmen , Millan Jose Luis , Poulet Blandine , Arnett Timothy , Orriss Isabel

Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse nucleotide triphosphates to the corresponding nucleotide monophosphate and the mineralisation inhibitor, pyrophosphate (PPi). This investigation examined the role of NPP1 in bone and soft tissue mineralisation using a mouse model lacking NPP1(Enpp1−/−). At physiological pH 7.35, cultured Enpp1−/...

ba0001oc6.5 | Mineralisation and energy metabolism | ECTS2013

A protective role for FGF23 in local defence against disrupted arterial wall integrity?

Zhu Dongxing , Mackenzie Neil , Millan Jose Luis , Farquharson Colin , MacRae Vicky

Increasing interest is focusing on the role of the FGF-23/Klotho axis in mediating vascular calcification. However, the underpinning mechanisms have yet to be fully elucidated. Murine VSMCs were cultured in calcifying medium for a 21-day period. FGF-23 mRNA expression was significantly up-regulated by 7 days (1.63-fold; P<0.001), with a concomitant increase in protein expression. mRNA and protein expression of both FGFR1 and Klotho were confirmed. Increased FGF-23...

ba0001pp170 | Cell biology: osteoblasts and bone formation | ECTS2013

Calcium transport and phosphomonohydrolase activity by proteoliposomes harboring annexin V and alkaline phosphatase

Bolean Mayte , Simao Ana Maria , Kiffer-Moreira Tina , Hoylaerts Marc , Millan Jose Luis , Ciancaglini Pietro

The biomineralization process is initiated inside matrix vesicles (MVs), with phosphate and calcium ions crystallizing as hydroxyapatite. This process is accomplished by the activities of several proteins, such as annexins (e.g. AnxV) that mediates Ca2+ influx into MVs and tissue-nonspecific alkaline phosphatase (TNAP), a phosphomonohydrolase that uses ATP and PPi as substrates. Dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS...

ba0001pp234 | Cell biology: osteoclasts and bone resorption | ECTS2013

Do ecto-nucleotidases play a role in the regulation of osteoclast function?

Hajjawi Mark , MacRae Vicky , Huesa Carmen , Millan Jose Luis , Arnett Timothy , Orriss Isabel

Extracellular nucleotides stimulate both the formation and resorptive activity of osteoclasts. Ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) hydrolyse extracellular nucleotide triphosphates to their corresponding monophosphate and pyrophosphate (PPi). We investigated if osteoclasts express functional NPPs and whether Enpp1 gene deletion influenced osteoclast formation and activity. Osteoclasts were formed from the bone marrow of 8 and 15 week old knockou...

ba0003oc5.1 | Important pathways in bone biology and cancer | ECTS2014

In vivo efficacy of a pharmacological inhibitor of TNAP to prevent arterial calcification and its associated cardiac hypertrophy and mortality

Sheen Campbell , Chhea Thangchanthida , Pinkerton Antony , Jackson Michael , Millan Jose Luis

Medial vascular calcification (MVC) is a pathological condition common to a variety of diseases, including chronic kidney disease, diabetes, obesity, generalized arterial calcification of infancy, arterial calcification due to deficiency of CD73, and Keutel syndrome. These diseases share the common feature of tissue-nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. We developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells, ...

ba0001oc6.2 | Mineralisation and energy metabolism | ECTS2013

Deficiency of the bone mineralisation inhibitor NPP1 protects against obesity and diabetes

Huesa Carmen , Morton Nicholas M , Ferron Mathieu , Karsenty Gerard , Millan Jose Luis , Ahmed Faisal , Farquharson Colin , MacRae Vicky E

Bone has recently emerged as a novel endocrine organ regulating glucose metabolism. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralisation by generating the mineralisation inhibitor pyrophosphate. In clinical studies increased activity of NPP1 has been found in patients with insulin resistance, and it has been shown to directly inhibit the insulin receptor. We hypothesised that mice lacking NPP1 (Enpp1−/−) would exhibit im...

ba0007lb5 | (1) | ICCBH2019

Chronic recurrent multifocal osteomyelitis in children with hypophosphatasia explained by anti-inflammatory nucleotidase activity of tissue nonspecific alkaline phosphatase in mesenchymal and hematopoietic cells

Bessueille Laurence , Briolay Anne , Como Juna , Mansouri Cylia , Gleizes Marie , El Jamal Alaeddine , Buchet Rene , Dumontet Charles , Matera Eva-Laure , Mornet Etienne , Millan Jose Luis , Fonta Caroline , Magne David

Deficiency in tissue nonspecific alkaline phosphatase (TNAP) causes hypophosphatasia (HPP), which is mainly characterized by skeletal hypomineralization. TNAP promotes mineralization by dephosphorylating the mineralization inhibitor inorganic pyrophosphate (PPi), which is generated from adenosine triphosphate (ATP) by ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Chronic recurrent multifocal osteomyelitis (CRMO), a sterile bone auto-inflammatory disease, has been ...