PRP modulates expression of bone matrix proteins in vivo without long-term effects on bone formation

Bone ◽  
2006 ◽  
Vol 38 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Michael Thorwarth ◽  
Falk Wehrhan ◽  
Stefan Schultze-Mosgau ◽  
Jörg Wiltfang ◽  
Karl Andreas Schlegel
Keyword(s):  
Bone Formation ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Long Term Effects ◽  
Bone Matrix Proteins

scholarly journals Do ASARM peptides play a role in nephrogenic systemic fibrosis?

2015 ◽  
Vol 309 (9) ◽  
pp. F764-F769 ◽  
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.

Correlation between mRNA levels for bone cell proteins and bone formation in long bones of maturing rats

1991 ◽  
Vol 261 (3) ◽  
pp. E348-E353
Author(s):  
R. T. Turner ◽  
T. C. Spelsberg
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Bone Formation ◽  
Radial Growth ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Long Bones ◽  
Mrna Levels ◽  
Bone Matrix Proteins ◽  
Periosteal Cells

This report describes the relationship between bone formation and mRNA levels for selected bone proteins. Dynamic bone histomorphometry was used to measure bone formation in tibial periosteum of male rats from weanling (3 wk) to 52 wk old. Northern blot analysis of freshly isolated periosteal cells from the long bones was used to determine steady-state mRNA levels for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAP), the bone matrix proteins osteocalcin (BGP), and prepro-alpha-2 (I) chain of type 1 precollagen (collagen), the osteoblast marker enzyme alkaline phosphatase (AP), and the osteoblast-derived signaling factor (growth factor) transforming growth factor-beta (TGF-beta). Radial growth at the tibial diaphysis achieved a maximum value in 8-wk-old rats and decreased progressively with age thereafter. This age-related decrease in the radial growth rate was initially due to reduced osteoblast activity; however, in older rats (greater than 17 wk old) reduced osteoblast number contributed to the decrease in bone formation. There was a strong correlation between the steady-state mRNA level for collagen and the periosteal bone formation rate. In contrast, the mRNA levels for the other bone proteins were more weakly correlated (TGF-beta and AP) or not correlated (BGP). These results suggest that the decreased bone matrix synthesis by periosteal cells in long bones of maturing rats is due to decreased expression of genes for bone matrix proteins.

scholarly journals The Effects of Orbital Spaceflight on Bone Histomorphometry and Messenger Ribonucleic Acid Levels for Bone Matrix Proteins and Skeletal Signaling Peptides in Ovariectomized Growing Rats*

Endocrinology ◽  
1997 ◽  
Vol 138 (4) ◽  
pp. 1567-1576 ◽  
Author(s):  
Jason M. Cavolina ◽  
Glenda L. Evans ◽  
Steven A. Harris ◽  
Minzhi Zhang ◽  
Kim C. Westerlind ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Ovariectomized Rats ◽  
Mrna Levels ◽  
Bone Area ◽  
Bone Matrix Proteins ◽  
Signaling Peptides

Abstract A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-α2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-β, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

scholarly journals A novel gelatin/chitooligosaccharide/demineralized bone matrix composite scaffold and periosteum-derived mesenchymal stem cells for bone tissue engineering

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Thakoon Thitiset ◽  
Siriporn Damrongsakkul ◽  
Supansa Yodmuang ◽  
Wilairat Leeanansaksiri ◽  
Jirun Apinun ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Alp Activity

Abstract Background A novel biodegradable scaffold including gelatin (G), chitooligosaccharide (COS), and demineralized bone matrix (DBM) could play a significant part in bone tissue engineering. The present study aimed to investigate the biological characteristics of composite scaffolds in combination of G, COS, and DBM for in vitro cell culture and in vivo animal bioassays. Methods Three-dimensional scaffolds from the mixture of G, COS, and DBM were fabricated into 3 groups, namely, G, GC, and GCD using a lyophilization technique. The scaffolds were cultured with mesenchymal stem cells (MSCs) for 4 weeks to determine biological responses such as cell attachment and cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, cell morphology, and cell surface elemental composition. For the in vivo bioassay, G, GC, and GCD, acellular scaffolds were implanted subcutaneously in 8-week-old male Wistar rats for 4 weeks and 8 weeks. The explants were assessed for new bone formation using hematoxylin and eosin (H&E) staining and von Kossa staining. Results The MSCs could attach and proliferate on all three groups of scaffolds. Interestingly, the ALP activity of MSCs reached the greatest value on day 7 after cultured on the scaffolds, whereas the calcium assay displayed the highest level of calcium in MSCs on day 28. Furthermore, weight percentages of calcium and phosphorus on the surface of MSCs after cultivation on the GCD scaffolds increased when compared to those on other scaffolds. The scanning electron microscopy images showed that MSCs attached and proliferated on the scaffold surface thoroughly over the cultivation time. Mineral crystal aggregation was evident in GC and greatly in GCD scaffolds. H&E staining illustrated that G, GC, and GCD scaffolds displayed osteoid after 4 weeks of implantation and von Kossa staining confirmed the mineralization at 8 weeks in G, GC, and GCD scaffolds. Conclusion The MSCs cultured in GCD scaffolds revealed greater osteogenic differentiation than those cultured in G and GC scaffolds. Additionally, the G, GC, and GCD scaffolds could promote in vivo ectopic bone formation in rat model. The GCD scaffolds exhibited maximum osteoinductive capability compared with others and may be potentially used for bone regeneration.

scholarly journals 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

1996 ◽  
Vol 75 (6) ◽  
pp. 811-823 ◽  
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.

scholarly journals Long-term effects of carbon containing engineered nanomaterials and asbestos in the lung: one year postexposure comparisons

2014 ◽  
Vol 306 (2) ◽  
pp. L170-L182 ◽  
Author(s):  
Anna A. Shvedova ◽  
Naveena Yanamala ◽  
Elena R. Kisin ◽  
Alexey V. Tkach ◽  
Ashley R. Murray ◽  
...  
Keyword(s):  
Lung Tumor ◽  
Inhalation Exposure ◽  
Geometric Feature ◽  
Width Ratio ◽  
Long Term Effects ◽  
Genotoxic Effects ◽  
Pulmonary Exposure ◽  
Pharyngeal Aspiration

The hallmark geometric feature of single-walled carbon nanotubes (SWCNT) and carbon nanofibers (CNF), high length to width ratio, makes them similar to a hazardous agent, asbestos. Very limited data are available concerning long-term effects of pulmonary exposure to SWCNT or CNF. Here, we compared inflammatory, fibrogenic, and genotoxic effects of CNF, SWCNT, or asbestos in mice 1 yr after pharyngeal aspiration. In addition, we compared pulmonary responses to SWCNT by bolus dosing through pharyngeal aspiration and inhalation 5 h/day for 4 days, to evaluate the effect of dose rate. The aspiration studies showed that these particles can be visualized in the lung at 1 yr postexposure, whereas some translocate to lymphatics. All these particles induced chronic bronchopneumonia and lymphadenitis, accompanied by pulmonary fibrosis. CNF and asbestos were found to promote the greatest degree of inflammation, followed by SWCNT, whereas SWCNT were the most fibrogenic of these three particles. Furthermore, SWCNT induced cytogenetic alterations seen as micronuclei formation and nuclear protrusions in vivo. Importantly, inhalation exposure to SWCNT showed significantly greater inflammatory, fibrotic, and genotoxic effects than bolus pharyngeal aspiration. Finally, SWCNT and CNF, but not asbestos exposures, increased the incidence of K-ras oncogene mutations in the lung. No increased lung tumor incidence occurred after 1 yr postexposure to SWCNT, CNF, and asbestos. Overall, our data suggest that long-term pulmonary toxicity of SWCNT, CNF, and asbestos is defined, not only by their chemical composition, but also by the specific surface area and type of exposure.

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