Osteomimicry of Mammary Adenocarcinoma Cells In Vitro; Increased Expression of Bone Matrix Proteins and Proliferation within a 3D Collagen Environment

We investigated the expression of osteocalcin (OC), bone sialoprotein (BSP), osteonectin (ON), and alkaline phosphatase (ALP) during cell differentiation and bone nodule formation by fetal rat calvaria cells, using immunofluorescent and immunogold techniques at light and electron microscopic levels. Six hours after plating all proteins were expressed in calvaria cells. However, expression was not detected during the proliferation phase after plating. Cell morphological modifications were observed in osteoblastic cells expressing ALP, OC, and BSP, but not ON. During the matrix formation phase, all proteins were expressed with various intensities and OC was limited to differentiated osteoblastic cells. EM observations demonstrated that BSP was selectively associated with clusters of needle-like crystals, but not with collagen fibers, in mineralization foci and in the mineralized matrix. OC was localized intracellularly and in all the extracellular compartments, and was concentrated at the mineralization front. ON was distributed uniformly throughout the osteoid and mineralized matrix, which was intensely labeled. The results show that the expression of bone matrix proteins during differentiation of calvaria cells and nodule formation in vitro duplicate what is observed during osteogenesis in vivo.

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Expression of bone matrix proteins associated with mineralized tissue formation by adult rat bone marrow cells in vitro: Inductive effects of dexamethasone on the osteoblastic phenotype

Journal of Cellular Physiology ◽

10.1002/jcp.1041470115 ◽

1991 ◽

Vol 147 (1) ◽

pp. 111-120 ◽

Cited By ~ 175

Author(s):

Shohei Kasugai ◽

Reynaldo Todescan ◽

Toshihiko Nagata ◽

Kam-Ling Yao ◽

William T. Butler ◽

...

Keyword(s):

Bone Marrow Cells ◽

Bone Matrix ◽

Matrix Proteins ◽

Tissue Formation ◽

Mineralized Tissue ◽

Adult Rat ◽

Osteoblastic Phenotype ◽

Bone Matrix Proteins ◽

Inductive Effects

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Do ASARM peptides play a role in nephrogenic systemic fibrosis?

AJP Renal Physiology ◽

10.1152/ajprenal.00201.2015 ◽

2015 ◽

Vol 309 (9) ◽

pp. F764-F769 ◽

Cited By ~ 5

Author(s):

Peter S. N. Rowe ◽

Lesya V. Zelenchuk ◽

Jennifer S. Laurence ◽

Phil Lee ◽

William M. Brooks ◽

...

Keyword(s):

Nephrogenic Systemic Fibrosis ◽

Bone Mineralization ◽

Bone Matrix ◽

Matrix Proteins ◽

Hypophosphatemic Rickets ◽

Bone Matrix Proteins ◽

Risk Of Disease ◽

Asarm Peptide

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3+)-based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3+ from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3+ release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE-associated peptides (ASARM peptides) induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind Ca2+ and hydroxyapatite. Since the ionic radius of Gd3+ is close to that of Ca2+, we hypothesized that ASARM peptides increase the risk of NSF by inducing release of Gd3+ from GBCAs. Here, we show 1) ASARM peptides bind and induce release of Gd3+ from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the Gd3+-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-like pathology in a murine model with increased ASARM peptide (Hyp mouse). We conclude ASARM peptides may play a role in NSF and SPR4 peptide is a candidate adjuvant for preventing or reducing risk of disease.

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Evaluation of osteocalcin and other bone matrix proteins as markers of the osteoblastic phenotype in vitro

Bone ◽

10.1016/8756-3282(85)90244-3 ◽

1985 ◽

Vol 6 (6) ◽

pp. 472

Author(s):

J.A. Gallagher ◽

J.N. Beresford ◽

H. Skojdt ◽

M. Couch ◽

J.W. Poser ◽

...

Keyword(s):

Bone Matrix ◽

Matrix Proteins ◽

Osteoblastic Phenotype ◽

Bone Matrix Proteins

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Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)98430-9 ◽

1993 ◽

Vol 268 (13) ◽

pp. 9901-9907

Author(s):

F.P. Ross ◽

J. Chappel ◽

J.I. Alvarez ◽

D. Sander ◽

W.T. Butler ◽

...

Keyword(s):

Bone Resorption ◽

Bone Matrix ◽

Bone Sialoprotein ◽

Matrix Proteins ◽

Bone Matrix Proteins ◽

Alpha V Beta 3

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Effect of protein restriction on the messenger RNA contents of bone-matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovariectomized rats

British Journal Of Nutrition ◽

10.1079/bjn19960188 ◽

1996 ◽

Vol 75 (6) ◽

pp. 811-823 ◽

Cited By ~ 10

Author(s):

Yusuke Higashi ◽

Asako Takenaka ◽

Shin-Ichiro Takahashi ◽

Tadashi Noguchi

Keyword(s):

Dietary Protein ◽

Type I Collagen ◽

Control Diet ◽

Bone Matrix ◽

Protein Restriction ◽

Matrix Proteins ◽

Type I ◽

Bone Matrix Proteins ◽

Mrna Content ◽

Insulin Like Growth Factors

It has been reported that loss of ovarian oestrogen after menopause or by ovariectomy causes osteoporosis. In order to elucidate the effect of dietary protein restriction on bone metabolism after ovariectomy, we fed ovariectomized young female rats on a casein-based diet (50g/kg diet (protein restriction) or 200g/kg diet (control)) for 3 weeks and measured mRNA contents of bone-matrix proteins such as osteocalcin, osteopontin and α1 type I collagen, insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in femur. Ovariectomy decreased the weight of fat-free dry bone and increased urinary excretion of pyridinium cross-links significantly, although dietary protein restriction did not affect them. Neither ovariectomy nor protein restriction affected the content of mRNA of osteopontin and osteocalcin; however, ovariectomy increased and protein restriction extensively decreased the α1 type I collagen mRNA content in bone tissues. Ovariectomy increased IGF-I mRNA only in the rats fed on the control diet. Conversely, protein rest riction increased and ovariectomy decreased the IGF-II mRNA content in femur. Furthermore, the contents of IGFBP-2, IGFBP-4 and IGFBP-5 mRNA increased, but the content of IGFBP-3 mRNA decreased in femur of the rats fed on the protein-restricted diet. In particular, ovariectomy decreased the IGFBP-2 mRNA content in the protein-restricted rats and the IGFBP-6 mRNA content in the rats fed on the control diet. These results clearly show that the mRNA for some of the proteins which have been shown to be involved in bone formation are regulated by both quantity of dietary proteins and ovarian hormones.

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