Bone Abstracts

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...

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...

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−/...

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...

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...

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...

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, ...

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...

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 ...