Factors affecting growth, differentiation and apoptosis of osteoblastic and osteosarcoma cells
Author: Li, Yan
Date: 2008-11-07
Location: M63, Karolinska universitetssjukhuset, Huddinge
Time: 09.00
Department: Institutionen för klinisk vetenskap / Department of Clinical Sciences
View/ Open:
Thesis (498.8Kb)
Abstract
Osteoblasts play a fundamental role in determining bone structure and function. These cells originate from mesenchymal stem cells (MSCs) and through proliferation and differentiation develop into preosteoblasts and then into mature cells. Most of these cells undergo apoptosis before reaching their terminal differentiated stages of either osteocytes or bone lining cells. These processes, i.e. proliferation, differentiation, and apoptosis, are affected by systemic hormones and local factors. In addition, there are exogenous regulators, which can either be natural substances or synthetic compounds.
This thesis describes investigations of the effects of several selected factors on proliferation, differentiation, and apoptosis of osteoblastic cells. The thesis is based on four papers: In the first paper, the effects of Sirt1 regulators, resveratrol (RSV), nicotinamide (NAM), and isonicotinamide (INM), on the commitment ofmesenchymal stem cells (MSC) were studied. We found that the Sirt1 activators, RSV and INM, inhibited adipocyte formation and enhanced osteoblast differentiation, while the inhibitor NAM had the opposite effect. In the second paper, osteoblastic cells from different origins, mouse, rat, and human, were treated with 1alpha,25(OH)2D3 and its analogue, 2-methylene-19-nor-(20S)- 1alpha,25(OH)2D3 (2MD). Species-dependent effects on cell growth and alkaline phosphatase (ALP) activity were clearly seen. In the third paper, we found that the expression of Interleukin-6 (IL-6) receptor increased during osteoblast differentiation. IL-6 acted as a differentiation accelerator in the early stage and an apoptosis inducer at late mature stage. In the forth paper, the effects of Sirt1 activators, RSV and INM, on proliferation and apoptosis of human osteosarcoma (OS) cells were studied. We found an inhibitory effect of Sirt1 activators on OS cells and showed a synergism between RSV and L-asparaginase (ASNase), which is a selective nutritional restrictor.
In summary, the work presented in this thesis provides new information about the effects of two osteoblast differentiation regulators, 1alpha,25(OH)2D3 and IL-6. Additionally, certain compounds affecting Sirt1 activity were found to influence osteoblast differentiation; RSV and INM which increase Sirt1 activity also had a profoundly negative effect on growth of OS cells in vitro.
This thesis describes investigations of the effects of several selected factors on proliferation, differentiation, and apoptosis of osteoblastic cells. The thesis is based on four papers: In the first paper, the effects of Sirt1 regulators, resveratrol (RSV), nicotinamide (NAM), and isonicotinamide (INM), on the commitment ofmesenchymal stem cells (MSC) were studied. We found that the Sirt1 activators, RSV and INM, inhibited adipocyte formation and enhanced osteoblast differentiation, while the inhibitor NAM had the opposite effect. In the second paper, osteoblastic cells from different origins, mouse, rat, and human, were treated with 1alpha,25(OH)2D3 and its analogue, 2-methylene-19-nor-(20S)- 1alpha,25(OH)2D3 (2MD). Species-dependent effects on cell growth and alkaline phosphatase (ALP) activity were clearly seen. In the third paper, we found that the expression of Interleukin-6 (IL-6) receptor increased during osteoblast differentiation. IL-6 acted as a differentiation accelerator in the early stage and an apoptosis inducer at late mature stage. In the forth paper, the effects of Sirt1 activators, RSV and INM, on proliferation and apoptosis of human osteosarcoma (OS) cells were studied. We found an inhibitory effect of Sirt1 activators on OS cells and showed a synergism between RSV and L-asparaginase (ASNase), which is a selective nutritional restrictor.
In summary, the work presented in this thesis provides new information about the effects of two osteoblast differentiation regulators, 1alpha,25(OH)2D3 and IL-6. Additionally, certain compounds affecting Sirt1 activity were found to influence osteoblast differentiation; RSV and INM which increase Sirt1 activity also had a profoundly negative effect on growth of OS cells in vitro.
List of papers:
I. Bäckesjö CM, Li Y, Lindgren U, Haldosen LA (2006). Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. J Bone Miner Res. 21(7): 993-1002.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Li Y, Bäckesjö CM, Haldosen LA, Lindgren U (2008). Species difference exists in the effects of 1alpha,25(OH)(2)D(3) and its analogue 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) (2MD) on osteoblastic cells. J Steroid Biochem Mol Biol. Sep 11.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Li Y, Bäckesjö CM, Haldosén LA, Lindgren U (2008). IL-6 receptor expression and IL-6 effects change during osteoblast differentiation. Cytokine. 43(2): 165-73.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Li Y, Bäckesjö CM, Haldosen LA, Lindgren U (2008). Resveratrol inhibits proliferation and promotes apoptosis of osteosarcoma cells. The European Journal of Pharmacology. [Accepted]
Fulltext (DOI)
Pubmed
View record in Web of Science®
I. Bäckesjö CM, Li Y, Lindgren U, Haldosen LA (2006). Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. J Bone Miner Res. 21(7): 993-1002.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Li Y, Bäckesjö CM, Haldosen LA, Lindgren U (2008). Species difference exists in the effects of 1alpha,25(OH)(2)D(3) and its analogue 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D(3) (2MD) on osteoblastic cells. J Steroid Biochem Mol Biol. Sep 11.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Li Y, Bäckesjö CM, Haldosén LA, Lindgren U (2008). IL-6 receptor expression and IL-6 effects change during osteoblast differentiation. Cytokine. 43(2): 165-73.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Li Y, Bäckesjö CM, Haldosen LA, Lindgren U (2008). Resveratrol inhibits proliferation and promotes apoptosis of osteosarcoma cells. The European Journal of Pharmacology. [Accepted]
Fulltext (DOI)
Pubmed
View record in Web of Science®
Issue date: 2008-10-17
Rights:
Publication year: 2008
ISBN: 978-91-7409-202-8
Statistics
Total Visits
Views | |
---|---|
Factors ...(legacy) | 902 |
Factors ... | 378 |
Total Visits Per Month
January 2024 | February 2024 | March 2024 | April 2024 | May 2024 | June 2024 | July 2024 | |
---|---|---|---|---|---|---|---|
Factors ... | 14 | 14 | 17 | 15 | 16 | 9 | 7 |
File Visits
Views | |
---|---|
thesis.pdf(legacy) | 1431 |
thesis.pdf | 325 |
thesis.pdf.txt(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 492 |
Sweden | 102 |
Ireland | 92 |
Germany | 61 |
United Kingdom | 60 |
China | 55 |
South Korea | 22 |
Russia | 21 |
Finland | 17 |
India | 14 |
Top cities views
Views | |
---|---|
Dublin | 92 |
Ashburn | 50 |
Sunnyvale | 37 |
Romeo | 33 |
Beijing | 20 |
Kiez | 17 |
Seoul | 17 |
Stockholm | 16 |
Helsinki | 10 |
London | 7 |