Searchable abstracts of presentations at key conferences on calcified tissues

ba0001pp27 | Arthritis and other joint diseases: translational and clinical | ECTS2013

Sclerostin/MEPE axis in OA: lessons from long bone development

Staines Katherine , Poulet Blandine , Farquharson Colin , Pitsillides Andrew

The re-initiation of developmental processes in osteoarthritis (OA) has emerged with similarities to endochondral ossification; responsible for long bone development. We aimed to establish the role of the Wnt inhibitor, sclerostin in endochondral ossification, and its relationship with MEPE, a calcification inhibitor with potential downstream functions. Knee joints from male Str/ort (spontaneous OA) and age-matched CBA control mice were analysed at 8, 18, and 40+ weeks of age ...

ba0001pp494 | Other diseases of bone and mineral metabolism | ECTS2013

BMP-9 induces the calcification of vascular smooth muscle cells

Zhu Dongxing , Mackenzie Neil , Farquharson Colin , MacRae Vicky

The process of vascular calcification shares many similarities with that of skeletal mineralisation, and involves the deposition of hydroxyapatite crystals in arteries and cardiac muscle. However, the cellular mechanisms responsible have yet to be fully elucidated. BMP-9 has been shown to exert direct effects on both bone development and vascular function. In the present study, we have investigated the role of BMP-9 in vascular smooth muscle cell (VSMC) calcification. Murine V...

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...

ba0006p151 | (1) | ICCBH2017

Characterisation of skeletal developmental in mouse models of Duchenne Muscular Dystrophy

Wood Claire , Wong Sze C , Straub Volker , Ahmed S Faisal , Farquharson Colin

Short stature and osteoporosis are common in DMD. Disease progression can be slowed by glucocorticoids but these are associated with further growth retardation and skeletal fragility. The defect in growth and skeletal development in children with DMD is probably multifactorial and not solely dependent on glucocorticoid exposure. The muscular dystrophy x-linked (mdx) mouse is the most commonly used animal model of DMD. However, its growth phenotype has not been studied...

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...

ba0005p60 | Bone development/growth and fracture repair | ECTS2016

Role of PHOSPHO1 in chondrocyte matrix vesicle mineralization: an AFM study

Bottini Massimo , Yadav Manisha , Bhattacharya Kunal , Magrini Andrea , Rosato Nicola , Fadeel Bengt , Farquharson Colin , Luis Millan Jose

We used atomic force microscopy (AFM) to study the morphology and development of mineralization-competent matrix vesicles (MVs) secreted by chondrocytes isolated from WT and Phospho1−/− mice in order to validate the role of PHOSPHO1 in MV mineralization. All MVs appeared as flattened globular features either individually dispersed or connected to a mat-like structure. The mat-like structure very closely resembled type-X collagen that has been de...

ba0001oc6.6 | Mineralisation and energy metabolism | ECTS2013

An emerging role of phospho1 in the regulation of energy metabolism

Oldknow Karla , Morton Nik Morton's , Yadav Manisha , Rajoanah Sophie , Huesa Carmen , Bunger Lutz , Ferron Mathieu , Karsenty Gerard , MacRae Vicky , Milan Jose Luis , Farquharson Colin

Genetic approaches to bone physiology utilising judicious gain and loss of function models have identified bone as an endocrine organ, being involved in the regulation of energy metabolism and reproduction. Recent advances expand our understanding and identify a new and unconventional role of bone beyond its classical functions. PHOSPHO1 is a bone specific phosphatase with a recognised role in bone mineralisation, but our present studies have now identified a novel role for PH...