Osteoblast-Stimulating Factor-1 (OSF-1) : a peptide with diverse roles in bone development
Osteoblast-Stimulating Factor-1 (OSF-1) : a peptide with diverse roles in bone development
In search for anabolic agents that enhance osteoblast activity, the role of a 136-amino acid cytokine, referred to as osteoblast-stimulating factor-1 (OSF-1), was examined in transgenic mice over-expressing the human osf-1 gene, and its effects analysed in vitro. In keeping with earlier reports on the function of OSF-1 in stimulating new bone formation, the protein was found localised at sites of new periosteal and endochondral ossification in bones of control and transgenic mice. OSF-1 was synthesized by osteoblasts during early stages of osteogenic differentiation and secreted into the bone matrix. Although over-expression did not result in larger animals, calcium content/ unit dry bone weight in transgenic mice was 10% higher than in control mice.
A distinct effect of osf-1 over-expression was the synthesis of the OSF-1 protein by growth plate and articular chondrocytes of only transgenic mice. Articular chondrocytes of transgenic mice were also found to synthesize Type 1 collagen, a bone-type protein. To confirm that over-expression of osf-1 had provided the stimulus, cartilaginous explants were cultured with recombinant OSF-1, which in turn induced Type 1 collagen synthesis by chondrocytes in vitro.
Expression of osf-1 was demonstrated by in situ hybridization in human and mouse bone marrow cell cultures. In vitro, recombinant OSF-1 enhanced osteogenic differentiation of mouse bone marrow cells at an appreciably low (10 pg/ml) concentration in comparison to recombinant bone morphogenetic protein-2 (rhBMP-2), which served as the positive control. However, unlike BMP-2, OSF-1 was not osteoinductive as it failed to divert the multipotent, pre-myoblastic C2C12 cells along the osteogenic lineage. Interactions with BMP-2, studied using C2C12 cells, revealed OSF-1 to be a BMP-2 antagonist if added together with BMP-2.
University of Southampton
Tare, Rahul Shrikant
b9bcf276-291a-49c3-b8da-a2bdc4bf8cff
2002
Tare, Rahul Shrikant
b9bcf276-291a-49c3-b8da-a2bdc4bf8cff
Tare, Rahul Shrikant
(2002)
Osteoblast-Stimulating Factor-1 (OSF-1) : a peptide with diverse roles in bone development.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
In search for anabolic agents that enhance osteoblast activity, the role of a 136-amino acid cytokine, referred to as osteoblast-stimulating factor-1 (OSF-1), was examined in transgenic mice over-expressing the human osf-1 gene, and its effects analysed in vitro. In keeping with earlier reports on the function of OSF-1 in stimulating new bone formation, the protein was found localised at sites of new periosteal and endochondral ossification in bones of control and transgenic mice. OSF-1 was synthesized by osteoblasts during early stages of osteogenic differentiation and secreted into the bone matrix. Although over-expression did not result in larger animals, calcium content/ unit dry bone weight in transgenic mice was 10% higher than in control mice.
A distinct effect of osf-1 over-expression was the synthesis of the OSF-1 protein by growth plate and articular chondrocytes of only transgenic mice. Articular chondrocytes of transgenic mice were also found to synthesize Type 1 collagen, a bone-type protein. To confirm that over-expression of osf-1 had provided the stimulus, cartilaginous explants were cultured with recombinant OSF-1, which in turn induced Type 1 collagen synthesis by chondrocytes in vitro.
Expression of osf-1 was demonstrated by in situ hybridization in human and mouse bone marrow cell cultures. In vitro, recombinant OSF-1 enhanced osteogenic differentiation of mouse bone marrow cells at an appreciably low (10 pg/ml) concentration in comparison to recombinant bone morphogenetic protein-2 (rhBMP-2), which served as the positive control. However, unlike BMP-2, OSF-1 was not osteoinductive as it failed to divert the multipotent, pre-myoblastic C2C12 cells along the osteogenic lineage. Interactions with BMP-2, studied using C2C12 cells, revealed OSF-1 to be a BMP-2 antagonist if added together with BMP-2.
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Published date: 2002
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Local EPrints ID: 464793
URI: http://eprints.soton.ac.uk/id/eprint/464793
PURE UUID: 9d2b8b1d-3029-485e-a4a1-acfb008220c2
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Date deposited: 05 Jul 2022 00:02
Last modified: 16 Mar 2024 19:45
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Author:
Rahul Shrikant Tare
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