Bone Abstracts

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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 ...

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...

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...

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...

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...

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...

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...