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Regulation of Osteoblast Differentiation - A Novel Function for FGF-8.

Valta, Maija P ; Hentunen, Teuvo ; Qu, Qiang ; Valve, Eeva M ; Harjula, Anna ; Seppänen, Jani A ; Väänänen, Kalervo H and Härkönen, Pirkko LU (2006) In Endocrinology 147(Jan 26). p.2171-2182
Abstract
Several members of the fibroblast growth factor (FGF) family have an important role in the development of skeletal tissues. FGF-8 is widely expressed in the developing skeleton, but its function there has remained unknown. We asked in this study whether FGF-8 could have a role in the differentiation of mesenchymal stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow cultures effectively increased initial cell proliferation as well as subsequent osteoblast-specific alkaline phosphatase production, bone nodule formation, and calcium accumulation if it was added to the cultures at an early stage of osteoblastic differentiation. Exogenous FGF-8 also stimulated the proliferation of MG63 osteosarcoma cells, which was... (More)
Several members of the fibroblast growth factor (FGF) family have an important role in the development of skeletal tissues. FGF-8 is widely expressed in the developing skeleton, but its function there has remained unknown. We asked in this study whether FGF-8 could have a role in the differentiation of mesenchymal stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow cultures effectively increased initial cell proliferation as well as subsequent osteoblast-specific alkaline phosphatase production, bone nodule formation, and calcium accumulation if it was added to the cultures at an early stage of osteoblastic differentiation. Exogenous FGF-8 also stimulated the proliferation of MG63 osteosarcoma cells, which was blocked by a neutralizing antibody to FGF-8b. In addition, the heparin-binding growth factor fraction of Shionogi 115 (S115) mouse breast cancer cells, which express and secrete FGF-8 at a very high level, had an effect in bone marrow cultures similar to that of exogenous FGF-8. Interestingly, experimental nude mouse tumors of S115 cells present ectopic bone and cartilage formation as demonstrated by typical histology and expression of markers specific for cartilage (type II and IX collagen) and bone (osteocalcin). These results demonstrate that FGF-8 effectively predetermines bone marrow cells to differentiate to osteoblasts and increases bone formation in vitro. It is possible that FGF-8 also stimulates bone formation in vivo. The results suggest that FGF-8, which is expressed by a great proportion of malignant breast and prostate tumors, may, among other factors, also be involved in the formation of osteosclerotic bone metastases. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrinology
volume
147
issue
Jan 26
pages
2171 - 2182
publisher
Oxford University Press
external identifiers
  • pmid:16439448
  • wos:000236830600016
  • scopus:33645890305
ISSN
0013-7227
DOI
10.1210/en.2005-1502
language
English
LU publication?
yes
additional info
Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:31.
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ead91eb3-b195-4cd6-aa9d-678a87f7db02 (old id 150109)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16439448&dopt=Abstract
date added to LUP
2016-04-01 12:11:48
date last changed
2021-08-18 05:20:34
@article{ead91eb3-b195-4cd6-aa9d-678a87f7db02,
  abstract     = {Several members of the fibroblast growth factor (FGF) family have an important role in the development of skeletal tissues. FGF-8 is widely expressed in the developing skeleton, but its function there has remained unknown. We asked in this study whether FGF-8 could have a role in the differentiation of mesenchymal stem cells to an osteoblastic lineage. Addition of FGF-8 to mouse bone marrow cultures effectively increased initial cell proliferation as well as subsequent osteoblast-specific alkaline phosphatase production, bone nodule formation, and calcium accumulation if it was added to the cultures at an early stage of osteoblastic differentiation. Exogenous FGF-8 also stimulated the proliferation of MG63 osteosarcoma cells, which was blocked by a neutralizing antibody to FGF-8b. In addition, the heparin-binding growth factor fraction of Shionogi 115 (S115) mouse breast cancer cells, which express and secrete FGF-8 at a very high level, had an effect in bone marrow cultures similar to that of exogenous FGF-8. Interestingly, experimental nude mouse tumors of S115 cells present ectopic bone and cartilage formation as demonstrated by typical histology and expression of markers specific for cartilage (type II and IX collagen) and bone (osteocalcin). These results demonstrate that FGF-8 effectively predetermines bone marrow cells to differentiate to osteoblasts and increases bone formation in vitro. It is possible that FGF-8 also stimulates bone formation in vivo. The results suggest that FGF-8, which is expressed by a great proportion of malignant breast and prostate tumors, may, among other factors, also be involved in the formation of osteosclerotic bone metastases.},
  author       = {Valta, Maija P and Hentunen, Teuvo and Qu, Qiang and Valve, Eeva M and Harjula, Anna and Seppänen, Jani A and Väänänen, Kalervo H and Härkönen, Pirkko},
  issn         = {0013-7227},
  language     = {eng},
  number       = {Jan 26},
  pages        = {2171--2182},
  publisher    = {Oxford University Press},
  series       = {Endocrinology},
  title        = {Regulation of Osteoblast Differentiation - A Novel Function for FGF-8.},
  url          = {http://dx.doi.org/10.1210/en.2005-1502},
  doi          = {10.1210/en.2005-1502},
  volume       = {147},
  year         = {2006},
}