Bone Abstracts

Deficiency of Cyclophilin B (CyPB) causes recessively inherited Type IX osteogenesis imperfecta, a moderately severe to lethal bone dysplasia. CyPB, encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that catalyzes the rate-limiting step in collagen folding, and also functions as a component of the collagen prolyl 3-hydroxylation complex. We previously demonstrated in a Ppib−/− mouse model that CyPB PPIase activity r...

OPTN encodes a cytoplasmic protein optineurin which has been shown to play a role in autophagy. Recent GWAS studies have shown that variants within OPTN are associated with the risk of Paget’s disease of bone, a disease characterized by focal areas of increased bone turnover due to increased osteoclast activity, suggesting a possible role of OPTN in the regulation of bone metabolism.The aim of this study was to investigate the role of optineurin in ...

Background: Elevated plasma homocysteine levels are a risk factor for osteoporotic fractures. Supplementation with vitamin B12/folic acid lowers homocysteine levels. This study aimed to determine whether vitamin B12/folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly.Methods: B-PROOF is a double-blind, randomized, placebo-controlled trial including 2 919 participants aged ≧65 years with elevated homocyste...

Delta-like 1/fetal antigen-1 (DLK1/FA1) is a negative regulator of bone mass in vivo as it inhibits osteoblast (OB) and stimulates osteoclast differentiation. However, the molecular mechanisms underlying these effects are not known. Thus, we studied the effect of DLK1/FA1 on different signaling pathways known to regulate OB differentiation. We identified DLK1/FA1 as an inhibitor of BMP2-induced OB differentiation. Stable overexpression of DLK1/FA1 in C2C12 cells or th...

The main cause of the bone destruction in rheumatoid arthritis (RA) is a destructive act of aggressively growing pannus, growth and angiogenesis of which are caused by the proliferation of fibroblasts in the synovium (S) due to the activation of fibroblast growth factor (FGF).Objectives: To reveal relationships of FGF with ultrasonic and arthroscopic and proliferative-destructive histological figures in RA.Methods: Complete compreh...

Chronic kidney disease (CKD) is defined according to the presence of kidney damage and level of kidney function – irrespective of the type of kidney disease (diagnosis). Among individuals with chronic kidney disease, the stages are defined based on the level of glomerular filtration rate. From infancy through young adulthood, the major causes of CKD arise from congenital abnormalities of the kidneys and urinary tract (CAKUT), acquired or congenital forms of nephrotic synd...

In advanced ER+ve breast cancer, the propensity of bone involvement is 85%. Similarly in advanced lung cancer, 30–40% of patients develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available. We present herein the development of four mouse models of breast and lung cancer su...

Introduction: Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. Types VII–IX OI involve defects in the collagen prolyl 3-hydroxylation complex, which modifies α1(I)Pro986. PPIB encodes CyPB, a complex component with PPIase activity and the major isomerase facilitating collagen folding. We investigated the role of CyPB in collagen post-translational modifications a...

Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Cartilage tissue is avascular in nature and the microenvironment of cartilage is hypoxic. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. Receptor activator of nuclear factor-kappaB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. Hypoxia-induced enh...

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