Journal ArticleDOI
Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein
Guangbin Luo,Patricia Ducy,Marc D. McKee,Gerald J. Pinero,Evelyne M Loyer,Richard R. Behringer,Gerard Karsenty +6 more
TLDR
Mgp, a mineral-binding ECM protein3 synthesized by vascular smooth-muscle cells and chondrocytes, is the first inhibitor of calcification of arteries and cartilage to be characterized in vivo.Abstract:
Calcification of the extracellular matrix (ECM) can be physiological or pathological. Physiological calcification occurs in bone when the soft ECM is converted into a rigid material capable of sustaining mechanical force; pathological calcification can occur in arteries and cartilage and other soft tissues. No molecular determinant regulating ECM calcification has yet been identified. A candidate molecule is matrix GLA protein (Mgp), a mineral-binding ECM protein synthesized by vascular smooth-muscle cells and chondrocytes, two cell types that produce an uncalcified ECM. Mice that lack Mgp develop to term but die within two months as a result of arterial calcification which leads to blood-vessel rupture. Chondrocytes that elaborate a typical cartilage matrix can be seen in the affected arteries. Mgp-deficient mice additionally exhibit inappropriate calcification of various cartilages, including the growth plate, which eventually leads to short stature, osteopenia and fractures. These results indicate that ECM calcification must be actively inhibited in soft tissues. To our knowledge, Mgp is the first inhibitor of calcification of arteries and cartilage to be characterized in vivo.read more
Citations
More filters
Journal ArticleDOI
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
TL;DR: Cloned cDNA encoding Osf2/Cbfa1 is identified as an osteoblast-specific transcription factor and as a regulator of osteoblasts differentiation.
Journal ArticleDOI
osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
N. Bucay,Ildiko Sarosi,Colin R. Dunstan,Sean Morony,John E. Tarpley,C. Capparelli,S. Scully,Hong Lin Tan,Weilong Xu,David L. Lacey,William J. Boyle,William S. Simonet +11 more
TL;DR: It is demonstrated that OPG is a critical regulator of postnatal bone mass and regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.
Journal ArticleDOI
XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response
TL;DR: It is suggested that the IRE1/XBP-1 pathway is required for efficient protein folding, maturation, and degradation in the ER and imply the existence of subsets of UPR target genes as defined by their dependence on XBP- 1.
Journal ArticleDOI
Biological and medical significance of calcium phosphates.
TL;DR: Calcium phosphates have a great biological and medical significance and in this review, an overview of the current knowledge in this subject is given.
Journal ArticleDOI
Chronic Kidney Disease Effects on the Cardiovascular System
TL;DR: Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease, which may lead to increased morbidity and mortality as a result of cardiovascular events.
References
More filters
Journal ArticleDOI
The pathogenesis of atherosclerosis: a perspective for the 1990s
TL;DR: The ability to control the expression of genes encoding these molecules and to target specific cell types provides opportunities to develop new diagnostic and therapeutic agents to induce the regression of the lesions and, possibly, to prevent their formation.
Journal ArticleDOI
Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells
Andrew S. Plump,Jonathan D. Smith,Tony Hayek,K Aalto-Setälä,Annemarie Walsh,Judy G. Verstuyft,Edward M. Rubin,Jan L. Breslow +7 more
TL;DR: apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis.
Journal ArticleDOI
Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein E
TL;DR: Apolipoprotein E-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis, with severe yet viable phenotype that should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.
Journal ArticleDOI
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice
TL;DR: It is demonstrated that src is not required for general cell viability (possibly because of functional overlap with other tyrosine kinases related to src) and an essential role for src in bone formation is uncovered.
Journal ArticleDOI
Regulation of Rate of Cartilage Differentiation by Indian Hedgehog and PTH-Related Protein
Andrea Vortkamp,Kaechoong Lee,Beate Lanske,Gino V. Segre,Henry M. Kronenberg,Clifford J. Tabin +5 more
TL;DR: In vitro application of Hedgehog or P THrP protein to normal or PTHrP (−/−) limb explants demonstrated that PTHRP mediates the effects of Ihh through the formation of a negative feedback loop that modulates the rate of chondrocyte differentiation.