Regulation and function of mineralized tissue extra-cellular matrix proteins : studies of ADAMTS-1 and osteoadherin
Author: Rehn, Anders
Date: 2008-06-04
Location: Hörsal 4U, Alfred Nobels Allé 8, Huddinge
Time: 09.00
Department: Institutionen för odontologi / Department of Odontology
View/ Open:
thesis.pdf (1.705Mb)
Abstract
The extracellular matrix of tissues is governed and maintained by cells
and a number of associated proteins. The extracellular matrix of the
skeleton is highly specialized, in that it is mineralized and contains
matrix-specific proteins with unique functions. Recent advances in
mineralized tissue research have identified novel functions for the
extracellular matrix molecules; from mere structural components to
regulators of tissue maintenance and endocrine homeostasis. Osteoblasts
and odontoblasts, the mineral matrix-forming cells of the skeleton and
teeth, differentiate from mesenchyme progenitors. In signaling of
differentiation into mature cells, the main switch towards osteoblast and
odontoblast differentiation and bone formation is achieved by the
signaling of bone morphogenetic proteins.
Inhibitory or stimulatory signaling by several factors result in the expression of proteins and factors which are necessary for the progression towards the mature cellular phenotype. Mature mineralized tissue producing cells secrete the collagen matrix which later becomes mineralized by hydroxyapatite. In addition, these cells also secrete the non-collagenous proteins of the mineralized tissue matrix that become incorporated into the matrix. The function of many of these proteins has been studied extensively and an understanding of their effect on matrix and cellular maintenance is now emerging.
Two proteins that are produced and secreted by osteoblasts and/or odontoblasts were investigated within the scope for this thesis: osteoadherin and ADAMTS-1. With an emphasis on regulation and function, it was possible to determine that osteoadherin is upregulated by terminally differentiated osteoblast and that osteoadherin affects cellular migration, proliferation and differentiation. The regulation of osteoadherin by neurotrophins in both osteoblasts and dental pulp cells suggests that a complex signaling network occurs during the development of tissue maturation. ADAMTS-1 is a multifunctional enzyme with disintegrin, thrombospondin and metalloproteinase domains. It was determined that ADAMTS-1 is upregulated by parathyroid hormone and associates with collagen and degrades it, and further that the catalytically active enzyme promotes cellular colonization of the 3D environment.
In summary, the work presented in this thesis provides novel understandings for the role of extracellular matrix proteins in determining the behavior of mineralized tissue cells.
Inhibitory or stimulatory signaling by several factors result in the expression of proteins and factors which are necessary for the progression towards the mature cellular phenotype. Mature mineralized tissue producing cells secrete the collagen matrix which later becomes mineralized by hydroxyapatite. In addition, these cells also secrete the non-collagenous proteins of the mineralized tissue matrix that become incorporated into the matrix. The function of many of these proteins has been studied extensively and an understanding of their effect on matrix and cellular maintenance is now emerging.
Two proteins that are produced and secreted by osteoblasts and/or odontoblasts were investigated within the scope for this thesis: osteoadherin and ADAMTS-1. With an emphasis on regulation and function, it was possible to determine that osteoadherin is upregulated by terminally differentiated osteoblast and that osteoadherin affects cellular migration, proliferation and differentiation. The regulation of osteoadherin by neurotrophins in both osteoblasts and dental pulp cells suggests that a complex signaling network occurs during the development of tissue maturation. ADAMTS-1 is a multifunctional enzyme with disintegrin, thrombospondin and metalloproteinase domains. It was determined that ADAMTS-1 is upregulated by parathyroid hormone and associates with collagen and degrades it, and further that the catalytically active enzyme promotes cellular colonization of the 3D environment.
In summary, the work presented in this thesis provides novel understandings for the role of extracellular matrix proteins in determining the behavior of mineralized tissue cells.
List of papers:
I. Rehn AP, Chalk AM, Wendel M (2006). "Differential regulation of osteoadherin (OSAD) by TGF-beta1 and BMP-2." Biochem Biophys Res Commun 349(3): 1057-64.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Rhen AP, Kaukua N, Persson AK, Sugars RV, Wendel M, Fried K (2008). "Neurotrophins upregulate OSAD and enhances differentiation of immature osteoblasts." [Submitted]
III. Rehn AP, Birch MA, Karlström E, Wendel M, Lind T (2007). "ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing." Bone 41(2): 231-8.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Rehn AP, Cerny R, Sugars RV, Kaukua N, Wendel M (2008). "Osteoadherin (OSAD) is upregulated by mature osteoblasts and enhances their in vitro differentiation and mineralization." Calcified Tissue International. [Accepted]
Fulltext (DOI)
Pubmed
View record in Web of Science®
I. Rehn AP, Chalk AM, Wendel M (2006). "Differential regulation of osteoadherin (OSAD) by TGF-beta1 and BMP-2." Biochem Biophys Res Commun 349(3): 1057-64.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Rhen AP, Kaukua N, Persson AK, Sugars RV, Wendel M, Fried K (2008). "Neurotrophins upregulate OSAD and enhances differentiation of immature osteoblasts." [Submitted]
III. Rehn AP, Birch MA, Karlström E, Wendel M, Lind T (2007). "ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing." Bone 41(2): 231-8.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Rehn AP, Cerny R, Sugars RV, Kaukua N, Wendel M (2008). "Osteoadherin (OSAD) is upregulated by mature osteoblasts and enhances their in vitro differentiation and mineralization." Calcified Tissue International. [Accepted]
Fulltext (DOI)
Pubmed
View record in Web of Science®
Issue date: 2008-05-14
Rights:
Publication year: 2008
ISBN: 978-91-7409-023-9
Statistics
Total Visits
Views | |
---|---|
Regulation ...(legacy) | 657 |
Regulation ... | 158 |
Total Visits Per Month
January 2024 | February 2024 | March 2024 | April 2024 | May 2024 | June 2024 | July 2024 | |
---|---|---|---|---|---|---|---|
Regulation ... | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
File Visits
Views | |
---|---|
thesis.pdf(legacy) | 424 |
thesis.pdf | 284 |
thesis.pdf.txt(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 366 |
Sweden | 66 |
China | 59 |
Germany | 52 |
South Korea | 24 |
Finland | 15 |
Russia | 12 |
France | 8 |
Denmark | 7 |
United Kingdom | 7 |
Top cities views
Views | |
---|---|
Ashburn | 48 |
Sunnyvale | 26 |
Beijing | 24 |
Romeo | 23 |
Kiez | 17 |
Seoul | 15 |
Stockholm | 11 |
Helsinki | 9 |
London | 7 |
Ballerup | 6 |