Bone Abstracts

Prolyl hydroxylase 2 (PHD2) regulates hypoxia-inducible factor α (HIFα) transcription factors and thus, erythropoietin (EPO) production. Under normoxic conditions, HIFα is constantly inactivated through hydroxylation by PHD2. Due to the embryonic lethality of PHD2 knock-out mice, its precise role in erythropoiesis and tissue homeostasis has long remained unknown. Recently, we generated a conditional knock-out (cKO) mouse lacking PHD2 in EPO-producing cells. Thes...

Extracellular nucleotides, signalling through P2 receptors, play a significant role in bone biology. ATP and ADP act via the P2Y1 or P2Y12 receptors to promote osteoclast formation and activity. Bone cells express the P2Y2 receptor and, in osteoblasts, it plays a role in regulating bone mineralisation. This investigation examined the role of the P2Y2 receptor in osteoclasts. Primary osteoclasts were isolated from the bone ma...

Thyrotoxicosis results in osteoporosis, and thyroid hormone (T3) stimulates osteoclastic bone resorption by unknown mechanisms. We previously demonstrated that knockout mice lacking thyroid hormone receptor α (TRα0/0) are euthyroid but have high bone mass, whereas mice lacking TRβ (TRβ−/−) are thyrotoxic and osteoporotic. Tartrate resistant acid phosphatase (TRAcP) staining revealed osteoclast numbers were reduced by 13% (<...

TNF receptor-associated factors (TRAFs) −6 and −3 regulate RANKL and TNF signaling in osteoclast precursors (OCPs), but they can have opposing effects, and it is not known if their functions are inter-dependent. For example, TRAF6 is required for RANKL/RANK-induced osteoclastogenesis, while TRAF3 limits both RANKL- and TNF-induced osteoclastogenesis through proteasomal degradation of NF-κB-inducing kinase; and inhibition of autophagic degradation of TRAF3 by c...

Objectives: A role for the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in controlling bone mass and strength has previously been reported. However, lack of one gut hormone is compensated by an elevated sensitivity to the other in single receptor knockout mice. As such the exact role of GIP and GLP-1 in bone is unclear. The aims of the present study were to assess bone mass and strength in mice with functional deletion of ...

Epidemiological studies suggest that patients using proton pump inhibitors (PPIs) have increased fracture risk. We have previously shown that H+/K+ATPase beta-subunit knockout (KO) mice have reduced BMD, BMC and mechanical bone strength compared to WT. Like users of PPIs, these mice have elevated serum gastrin levels due to high gastric pH. We wanted to study whether elevated gastrin influences bone quality in these mice.Female KO and WT mice aged 6 week...