Osteostatins
Definition
Osteostatin (OSN) is a fragment of parathyroid hormone-related protein (PTHrP) 107-111, which is responsible for a range of activities related to the modulation of bone formation as well as keratinocyte proliferation 1.
Related Peptides
OSN is a fragment potent inhibitor of osteoclastic bone resorption in rat 2. The hypercalcaemic activity of PTHrP is based on its partial homology to parathyroid hormone (PTH), a protein that regulates calcium homeostasis 3.
Discovery
PTHrP was originally discovered as a systemic humoral factor that is released by tumor cells and causes hypercalcaemia of malignancy (HHM) by Suva et al., in 1987 3.
Structural Characteristics
PTHrP is an important regulator of bone remodeling. Recent studies show that this protein can induce osteogenic features through its N- and C-terminal domains. Silica-based ordered mesoporous bioceramics with an SBA-15 structure known to be bioactive and biocompatible have recently been evaluated for their capacity to uptake and deliver L-tryptophan. This amino acid corresponds to the end position of the 107-111 domain (called osteostatin) of the native C-terminal PTHrP (107-139) fragment, whose true action in bone metabolism is still ill-defined4. Osteostatin (1-5) amide (human, bovine, dog, horse, mouse, rabbit, rat) H-Thr-Arg-Ser-Ala-Trp-NH2. This pTH-related protein fragment stimulated membrane-associated protein kinase C in freshly isolated rat spleen lymphocytes and thus raises the possibility of being a physiological regulator of the proliferation and other activities of lymphocytes 5.
Mode of Action
OSN has an inhibitory effect on bone resorption in vitro and in vivo. It exerts its inhibitory effect in a biphasic manner on TRAcP activity, inhibiting its secretion and either suppressing its synthesis or increasing its degradation. In addition, osteostatin induced rapid cellular retraction of both human and rat cultured osteoclasts, which was morphologically distinct from that produced by calcitonin6. Osteostatin also bears a number of phosphorylation sites that are important for the mitogenic activity of PTHrP in vascular smooth muscle cells 7.
Functions
OSN has been shown to inhibit bone resorption in rodents both in vitro and in vivo. In addition, local injection of low doses of one of these peptides to mouse calvaria decreases the number of osteoblasts, while intermittent administration of high doses of osteostatin into ovariectomized rats decreases trabecular bone formation, but restores cortical bone mass. Another function of OSN is that it increases the VEGF that has potential implications for both bone vascularization and bone formation, and neoangiogenesis in PTHrP-producing tumors 8. Anti-mitogenic properties of OSN have been detected in breast cancer cells and cytosolic calcium is used by OSN to signal in some neurons through a non-PTH receptor, unlike the separate circulating N-terminal domain 1.
References
1.Cuthbertson RM, Kemp BE, Barden JA (1999). Structure study of osteostatin PTHrP[Thr107](107-139). Biochim Biophys Acta., 1432(1):64-72.
2.Wang DX, Han R, Liu HY, Huang L, Fu J (1999). An Efficient Synthesis and Screening of Osteostatin analogues by Using Pooling Strategy. Chinese Chemical Letters, 10(10):821-824.
References and further reading may be available for this article. To view references and further reading you must purchase this article.
3.Dittmer J (2004). The importance of PTHrP for cancer development. Gene Ther Mol Biol., 8:451-464.
4.Lozano D, Manzano M, Doadrio JC, Salinas AJ, Vallet-Regí M, Gómez-Barrena E, Esbrit P (2009). Osteostatin-loaded bioceramics stimulate osteoblastic growth and differentiation. Acta Biomaterialia.
5.Whitfield JF, Isaacs RJ, Chakravarthy BR, Durkin JP, Morley P, Neugebauer W, Williams RE, Willick G, Rixon GH (1994). C-terminal fragments of parathyroid hormone-related protein, PTHrP-(107-111) and (107-139), and the N-terminal PTHrP-(1-40) fragment stimulate membrane-associated protein kinase C activity in rat spleen lymphocytes. J. Cell. Physiol. 158:518-522.
6.Zheng MH, McCaughan HB, Papadimitriou JM, Nicholson GC, Wood DJ (2004). Tartrate resistant acid phosphatase activity in rat cultured osteoclasts is inhibited by a carboxyl terminal peptide (osteostatin) from parathyroid hormone-related protein. J Cellular Biochem., 54 (2): 145 - 153.
7.Fiaschi-Taesch N, Takane KK, Masters S, Lopez-Talavera JC, and Stewart AF (2004).
Parathyroid Hormone-Related Protein as a Regulator of pRb and the Cell Cycle in Arterial Smooth Muscle. Circulation, 110(2): 177- 185.
8.Esbrit P, Alvarez-Arroyo MV, De Miguel F, Martin O, Martinez ME and Caramelo C (2000). C-Terminal Parathyroid Hormone-Related Protein Increases Vascular Endothelial Growth Factor in Human Osteoblastic Cells. J Am Soc Nephrol., 11:1085-1092.
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Osteostatin (OSN) is a fragment of parathyroid hormone-related protein (PTHrP) 107-111, which is responsible for a range of activities related to the modulation of bone formation as well as keratinocyte proliferation 1.
Related Peptides
OSN is a fragment potent inhibitor of osteoclastic bone resorption in rat 2. The hypercalcaemic activity of PTHrP is based on its partial homology to parathyroid hormone (PTH), a protein that regulates calcium homeostasis 3.
Discovery
PTHrP was originally discovered as a systemic humoral factor that is released by tumor cells and causes hypercalcaemia of malignancy (HHM) by Suva et al., in 1987 3.
Structural Characteristics
PTHrP is an important regulator of bone remodeling. Recent studies show that this protein can induce osteogenic features through its N- and C-terminal domains. Silica-based ordered mesoporous bioceramics with an SBA-15 structure known to be bioactive and biocompatible have recently been evaluated for their capacity to uptake and deliver L-tryptophan. This amino acid corresponds to the end position of the 107-111 domain (called osteostatin) of the native C-terminal PTHrP (107-139) fragment, whose true action in bone metabolism is still ill-defined4. Osteostatin (1-5) amide (human, bovine, dog, horse, mouse, rabbit, rat) H-Thr-Arg-Ser-Ala-Trp-NH2. This pTH-related protein fragment stimulated membrane-associated protein kinase C in freshly isolated rat spleen lymphocytes and thus raises the possibility of being a physiological regulator of the proliferation and other activities of lymphocytes 5.
Mode of Action
OSN has an inhibitory effect on bone resorption in vitro and in vivo. It exerts its inhibitory effect in a biphasic manner on TRAcP activity, inhibiting its secretion and either suppressing its synthesis or increasing its degradation. In addition, osteostatin induced rapid cellular retraction of both human and rat cultured osteoclasts, which was morphologically distinct from that produced by calcitonin6. Osteostatin also bears a number of phosphorylation sites that are important for the mitogenic activity of PTHrP in vascular smooth muscle cells 7.
Functions
OSN has been shown to inhibit bone resorption in rodents both in vitro and in vivo. In addition, local injection of low doses of one of these peptides to mouse calvaria decreases the number of osteoblasts, while intermittent administration of high doses of osteostatin into ovariectomized rats decreases trabecular bone formation, but restores cortical bone mass. Another function of OSN is that it increases the VEGF that has potential implications for both bone vascularization and bone formation, and neoangiogenesis in PTHrP-producing tumors 8. Anti-mitogenic properties of OSN have been detected in breast cancer cells and cytosolic calcium is used by OSN to signal in some neurons through a non-PTH receptor, unlike the separate circulating N-terminal domain 1.
References
1.Cuthbertson RM, Kemp BE, Barden JA (1999). Structure study of osteostatin PTHrP[Thr107](107-139). Biochim Biophys Acta., 1432(1):64-72.
2.Wang DX, Han R, Liu HY, Huang L, Fu J (1999). An Efficient Synthesis and Screening of Osteostatin analogues by Using Pooling Strategy. Chinese Chemical Letters, 10(10):821-824.
References and further reading may be available for this article. To view references and further reading you must purchase this article.
3.Dittmer J (2004). The importance of PTHrP for cancer development. Gene Ther Mol Biol., 8:451-464.
4.Lozano D, Manzano M, Doadrio JC, Salinas AJ, Vallet-Regí M, Gómez-Barrena E, Esbrit P (2009). Osteostatin-loaded bioceramics stimulate osteoblastic growth and differentiation. Acta Biomaterialia.
5.Whitfield JF, Isaacs RJ, Chakravarthy BR, Durkin JP, Morley P, Neugebauer W, Williams RE, Willick G, Rixon GH (1994). C-terminal fragments of parathyroid hormone-related protein, PTHrP-(107-111) and (107-139), and the N-terminal PTHrP-(1-40) fragment stimulate membrane-associated protein kinase C activity in rat spleen lymphocytes. J. Cell. Physiol. 158:518-522.
6.Zheng MH, McCaughan HB, Papadimitriou JM, Nicholson GC, Wood DJ (2004). Tartrate resistant acid phosphatase activity in rat cultured osteoclasts is inhibited by a carboxyl terminal peptide (osteostatin) from parathyroid hormone-related protein. J Cellular Biochem., 54 (2): 145 - 153.
7.Fiaschi-Taesch N, Takane KK, Masters S, Lopez-Talavera JC, and Stewart AF (2004).
Parathyroid Hormone-Related Protein as a Regulator of pRb and the Cell Cycle in Arterial Smooth Muscle. Circulation, 110(2): 177- 185.
8.Esbrit P, Alvarez-Arroyo MV, De Miguel F, Martin O, Martinez ME and Caramelo C (2000). C-Terminal Parathyroid Hormone-Related Protein Increases Vascular Endothelial Growth Factor in Human Osteoblastic Cells. J Am Soc Nephrol., 11:1085-1092.
For more detail please visit here Bio-Synthesis
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Founded in 1984, Bio-Synthesis, Inc. was first known as OCS Laboratories. It was the first producer of commercially available synthetic DNA and, in 1985, became a producer of synthetic peptides. In 1989, OCS incorporated as Bio-Synthesis, Inc. and moved its laboratories to Lewisville, Texas. Today, BSI occupies 10,000 square feet of modern laboratory space (completed in 1995) located 20 miles from downtown Dallas and 10 miles from D/FW airport. Among the surrounding academic institutions are: University of Texas Southwestern Medical School (12 miles), University of North Texas (10 miles), and University of North Texas Health Science Center (25 miles). These universities provide excellent library resources. Since its inception, BSI has steadily expanded its product lines and services to meet the growing needs of the molecular biology community. It has maintained its position as an aggressive, innovative company in a highly competitive marketplace without sacrificing quality. In the beginning, our primary emphasis was on synthesizing high quality DNA primers and linkers, which were the initial uses of oligos. Today, newer technologies, such as gene construction, PCR, mutagenesis, combinatorial libraries, dye/adduct labeling, DNA microarrays, peptide-nucleic acid chimeras, etc. have challenged the molecular biology field. In response, BSI has branched into several related areas including DNA paternity testing, DNA HLA typing, PNA synthesis, genomic sequencing, fluorescence-based genotyping, custom organic synthesis and other molecular biology based applications.
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Not only has BSI continued to provide quality DNA products and services for the research community, but it has also become a world leader in providing custom peptide products and services. Using state-of-the-art solid phase peptide chemistries, BSI provides high quality custom peptides, performs carrier conjugations, antipeptide antibody production, antigenic peptide design, synthesis of long and/or modified peptides, MALDI TOF analysis, contract research, consultation services and more.
Biomedical researchers worldwide in universities, biotech companies, private clinics, and government agencies use products from Bio-Synthesis, Inc. in studies ranging from PCR diagnostics to cancer research and the Human Genome Project. Contact us to discover how BSI can customize products/services to suit your research requirements.
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Founded in 1984, Bio-Synthesis, Inc. was first known as OCS Laboratories. It was the first producer of commercially available synthetic DNA and, in 1985, became a producer of synthetic peptides. In 1989, OCS incorporated as Bio-Synthesis, Inc. and moved its laboratories to Lewisville, Texas. Today, BSI occupies 10,000 square feet of modern laboratory space (completed in 1995) located 20 miles from downtown Dallas and 10 miles from D/FW airport. Among the surrounding academic institutions are: University of Texas Southwestern Medical School (12 miles), University of North Texas (10 miles), and University of North Texas Health Science Center (25 miles). These universities provide excellent library resources. Since its inception, BSI has steadily expanded its product lines and services to meet the growing needs of the molecular biology community. It has maintained its position as an aggressive, innovative company in a highly competitive marketplace without sacrificing quality. In the beginning, our primary emphasis was on synthesizing high quality DNA primers and linkers, which were the initial uses of oligos. Today, newer technologies, such as gene construction, PCR, mutagenesis, combinatorial libraries, dye/adduct labeling, DNA microarrays, peptide-nucleic acid chimeras, etc. have challenged the molecular biology field. In response, BSI has branched into several related areas including DNA paternity testing, DNA HLA typing, PNA synthesis, genomic sequencing, fluorescence-based genotyping, custom organic synthesis and other molecular biology based applications.
The Research and Development Division comprises a number of Ph.D. and M.D. professionals with backgrounds in molecular biology, immunology, nucleic acids, peptide synthesis, general organic chemistry, and automated amino acid sequencing. The Molecular Biology Division is set up to handle most modern experimental procedures; the Immunology Division specializes in immunodiagnostic-based reagents.
Not only has BSI continued to provide quality DNA products and services for the research community, but it has also become a world leader in providing custom peptide products and services. Using state-of-the-art solid phase peptide chemistries, BSI provides high quality custom peptides, performs carrier conjugations, antipeptide antibody production, antigenic peptide design, synthesis of long and/or modified peptides, MALDI TOF analysis, contract research, consultation services and more.
Biomedical researchers worldwide in universities, biotech companies, private clinics, and government agencies use products from Bio-Synthesis, Inc. in studies ranging from PCR diagnostics to cancer research and the Human Genome Project. Contact us to discover how BSI can customize products/services to suit your research requirements.
For more detail please visit our About Us
Please Contact Us :
Address: 612 E. Main street
City: Lewisville
State: Texas
Country: USA
Postal Code: 75057
Phone Number: 972-420-8505
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BIO-SYNTHESIS
BIO-SYNTHESIS, INC., is a leading life science products company with over 20 years of experience in the design and synthesis of Custom Peptide, small molecules and reagents for small scale research and bulk pharmaceutical trials. Using state of the art technology in our well-equipped alaboratories.
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BIO-SYNTHESIS
BIO-SYNTHESIS, INC., is a leading life science products company with over 20 years of experience in the design and synthesis of Custom Peptide, small molecules and reagents for small scale research and bulk pharmaceutical trials. Using state of the art technology in our well-equipped laboratories.
Please visit our Blog on Blogspot Bio-Synthesis
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