Endocrine Abstracts

Advances in the understanding of hypophosphatemic disorders have identified a novel group of molecules (FGF23, PHEX, MEPE, DMP1) that have been implicated in osteoblast mineralisation directly.The specific binding of PHEX to MEPE regulates the release of ASARM peptides which have an inhibitory role. Current concepts are speculative and the functional role of MEPE in chondrocyte mineralisation remains largely undefined.Proximal tibiae from 3-week old wild...

Introduction: SOCS2 is an important negative regulator of post-natal growth, as demonstrated by the SOCS2 null overgrowth phenotype. We have used SOCS2−/− mice, alongside chondrocytes overexpressing SOCS2, to investigate the mode of action of SOCS2 at the epiphysis. SOCS2 maybe involved in growth retardation associated with chronic inflammatory disorders, therefore we studied LPS induced growth retardation in wild type (WT) and SOCS2−/−<...

Intermittent PTH therapy is currently the only anabolic therapy for osteoporosis. As the mineralisation of the extracellular matrix of bone is essential for normal function it is vital that the effects of PTH on key regulators of mineralisation are uncovered. Ablation of Alpl, Phospho1 or Smpd3 results in skeletal hypomineralisation and as such this study examined the effects of bovine (b)PTH 1–34 on their expression. MC3T3 (clone-14) osteoblast-like cells display tempora...

Introduction: GH signalling is essential for post-natal linear bone growth. The systemic/local mechanisms responsible for GH action remain unclear as the importance of liver derived IGF1 on linear growth has recently been challenged.Aim: To unravel the underlying mechanisms of linear bone growth we exploited the suppressor of cytokine signalling-2 (SOCS2) KO mice which have enhanced linear growth despite normal systemic IGF1 and GH levels.<p class="a...

GH is anabolic to the skeleton but its mode of action is unclear. Clues are available from the study of the suppressor of cytokine signalling-2 (SOCS2) KO mouse which has increased bone mass despite normal systemic IGF1 levels. Whilst suggesting direct GH effects on bone forming osteoblasts the precise signalling mechanisms remain unclear. The aims of this study were, therefore, to further detail the bone phenotype of SOCS2 KO mice and determine if GH promotes bone mass by mec...

Advances in genetic approaches to bone physiology have expanded our understanding of the mechanisms by which bone and energy homeostasis interact. PHOSPHO1, a bone specific phosphatase is essential for the initiation of bone mineralisation. Here we now show that Phospho1 ablation confers a remarkable protection against obesity and diabetes in mice. To understand the mechanism whereby Phospho1 impacts metabolism, microarray analysis of osteoblasts, the primary...