Focal mineralization defect during disodium etidronate treatment of calcinosis

1982 ◽  
Vol 34 (1) ◽  
pp. 224-228 ◽  
Author(s):  
Robert S. Weinstein
Keyword(s):  
Mineralization Defect

Intrinsic mineralization defect inHyp mouse osteoblasts

1998 ◽  
Vol 275 (4) ◽  
pp. E700-E708 ◽  
Author(s):  
Z. S. Xiao ◽  
M. Crenshaw ◽  
R. Guo ◽  
T. Nesbitt ◽  
M. K. Drezner ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Disease ◽  
Normal Mouse ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Diffusible Factor ◽  
Murine Homologue ◽  
Mineralization Defect ◽  
Inactivating Mutations

X-linked hypophosphatemia (XLH) is caused by inactivating mutations of PEX, an endopeptidase of uncertain function. This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 3′ Pex deletion has been documented. In the present study, we report that immortalized osteoblasts derived from the simian virus 40 (SV40) transgenic Hyp mouse (TMOb- Hyp) have an impaired capacity to mineralize extracellular matrix in vitro. Compared with immortalized osteoblasts from the SV40 transgenic normal mouse (TMOb-Nl), osteoblast cultures from the SV40 Hyp mouse exhibit diminished 45Ca accumulation into extracellular matrix (37 ± 6 vs. 1,484 ± 68 counts ⋅ min−1 ⋅ μg protein−1) and reduced formation of mineralization nodules. Moreover, in coculture experiments, we found evidence that osteoblasts from the SV40 Hyp mouse produce a diffusible factor that blocks mineralization of extracellular matrix in normal osteoblasts. Our findings indicate that abnormal PEX in osteoblasts is associated with the accumulation of a factor(s) that inhibits mineralization of extracellular matrix in vitro.

Three children with lower limb fractures and a mineralization defect: a novel bone fragility disorder?

Bone ◽  
2004 ◽  
Vol 35 (5) ◽  
pp. 1023-1028 ◽  
Author(s):  
Craig F.J. Munns ◽  
Frank Rauch ◽  
Rose Travers ◽  
Francis H. Glorieux
Keyword(s):  
Lower Limb ◽  
Bone Fragility ◽  
Lower Limb Fractures ◽  
Mineralization Defect ◽  
Limb Fractures

scholarly journals Degradation of MEPE, DMP1, and Release of SIBLING ASARM-Peptides (Minhibins): ASARM-Peptide(s) Are Directly Responsible for Defective Mineralization in HYP

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1757-1772 ◽  
Author(s):  
Aline Martin ◽  
Valentin David ◽  
Jennifer S. Laurence ◽  
Patricia M. Schwarz ◽  
Eileen M. Lafer ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Matrix Protein ◽  
Specific Binding ◽  
Osteoclast Differentiation ◽  
Hypophosphatemic Rickets ◽  
Western Blots ◽  
Dentin Matrix Protein ◽  
Coculture Model ◽  
Mineralization Defect ◽  
Asarm Peptide

Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) and DMP1 (dentin matrix protein 1) result in X-linked hypophosphatemic rickets (HYP) and autosomal-recessive hypophosphatemic-rickets (ARHR), respectively. Specific binding of PHEX to matrix extracellular phosphoglycoprotein (MEPE) regulates the release of small protease-resistant MEPE peptides [acidic serine- and aspartate-rich MEPE-associated motif (ASARM) peptides]. ASARM peptides are potent inhibitors of mineralization (minhibins) that also occur in DMP1 [MEPE-related small integrin-binding ligand, N-linked glycoprotein (SIBLING) protein]. It is not known whether these peptides are directly responsible for the mineralization defect. We therefore used a bone marrow stromal cell (BMSC) coculture model, ASARM peptides, anti-ASARM antibodies, and a small synthetic PHEX peptide (SPR4; 4.2 kDa) to examine this. Surface plasmon resonance (SPR) and two-dimensional 1H/15N nuclear magnetic resonance demonstrated specific binding of SPR4 peptide to ASARM peptide. When cultured individually for 21 d, HYP BMSCs displayed reduced mineralization compared with wild type (WT) (−87%, P < 0.05). When cocultured, both HYP and WT cells failed to mineralize. However, cocultures (HYP and WT) or monocultures of HYP BMSCs treated with SPR4 peptide or anti-ASARM neutralizing antibodies mineralized normally. WT BMSCs treated with ASARM peptide also failed to mineralize properly without SPR4 peptide or anti-ASARM neutralizing antibodies. ASARM peptide treatment decreased PHEX mRNA and protein (−80%, P < 0.05) and SPR4 peptide cotreatment reversed this by binding ASARM peptide. SPR4 peptide also reversed ASARM peptide-mediated changes in expression of key osteoclast and osteoblast differentiation genes. Western blots of HYP calvariae and BMSCs revealed massive degradation of both MEPE and DMP1 protein compared with the WT. We conclude that degradation of MEPE and DMP-1 and release of ASARM peptides are chiefly responsible for the HYP mineralization defect and changes in osteoblast-osteoclast differentiation.

Bone disease in prolonged parenteral nutrition: osteopenia without mineralization defect

1986 ◽  
Vol 44 (1) ◽  
pp. 89-98 ◽  
Author(s):  
M Shike ◽  
M E Shils ◽  
A Heller ◽  
N Alcock ◽  
V Vigorita ◽  
...  
Keyword(s):  
Parenteral Nutrition ◽  
Bone Disease ◽  
Mineralization Defect

scholarly journals Matrix Extracellular Phosphoglycoprotein (MEPE) Is a New Bone Renal Hormone and Vascularization Modulator

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4012-4023 ◽  
Author(s):  
Valentin David ◽  
Aline Martin ◽  
Anne-Marie Hedge ◽  
Peter S. N. Rowe
Keyword(s):  
Bone Turnover ◽  
X Chromosome ◽  
Murine Model ◽  
Metabolic Disorders ◽  
Osteoblastic Cells ◽  
Mineralization Defect ◽  
Normal Differentiation ◽  
Reduced Activity ◽  
Dependent Pathway ◽  
Matrix Extracellular Phosphoglycoprotein

Abstract Increased matrix extracellular phosphoglycoprotein (MEPE) expression occurs in several phosphate and bone-mineral metabolic disorders. To resolve whether MEPE plays a role, we created a murine model overexpressing MEPE protein (MEPE tgn) in bone. MEPE tgn mice displayed a growth and mineralization defect with altered bone-renal vascularization that persisted to adulthood. The growth mineralization defect was due to a decrease in bone remodeling, and MEPE tgn mice were resistant to diet-induced renal calcification. MEPE protein-derived urinary ASARM peptides and reduced urinary Ca X PO4 product mediated the suppressed renal calcification. Osteoblastic cells displayed reduced activity but normal differentiation. Osteoclastic precursors were unable to differentiate in the presence of osteoblasts. In the kidney, NPT2a up-regulation induced an increase in phosphate renal reabsorption, leading to hyperphosphatemia. We conclude MEPE and MEPE-phosphate-regulating gene with homologies to endopeptidases on the X chromosome (MEPE-PHEX) interactions are components to an age-diet-dependent pathway that regulates bone turnover and mineralization and suppresses renal calcification. This novel pathway also modulates bone-renal vascularization and bone turnover.

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