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Cited by 138Bone Metabolism and DiseasesAlkaline Phosphatase Research StudiesTGF-β signaling in diseases

TGFβ alters growth and differentiation related gene expression in proliferating osteoblasts in vitro, preventing development of the mature bone phenotype

Breen, Ellen C., Ignotz, Ronald A., McCabe, Laura, Stein, Janet L., Stein, Gary S., Lian, Jane B.·1994·Journal of Cellular Physiology
DOI 10.1002/jcp.1041600214
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Abstract

This study examines the mechanism by which TGF‐β1, an important mediator of cell growth and differentiation, blocks the differentiation of normal rat diploid fetal osteoblasts in vitro. We have established that the inability for pre‐osteoblasts to differentiate is associated with changes in the expression of cell growth, matrix forming, and bone related genes. These include histone, jun B, c‐fos, collagen, fibronectin, osteocalcin, alkaline phosphatase, and osteopontin. Morphologically, the TGF‐β1‐treated osteoblasts exhibit an elongated, spread shape as opposed to the characteristic cuboidal appearance during the early stages of growth. This is followed by a decrease in the number of bone nodules formed and the amount of calcium deposition. These effects on differentiation can occur without dramatic changes in cell growth if TGF‐β1 is given for a short time early in the proliferative phase. However, continuous exposure to TGF‐β1 leads to a bifunctional growth response from a negative effect during the proliferative phase to a positive growth effect during the later matrix maturation and mineralization phases of the osteoblast developmental sequence. Extracellular matrix genes, fibronectin, osteopontin and α1(I) collagen, are altered in their expression pattern which may provide an aberrant matrix environment for mineralization and osteoblast maturation and potentiate the TGF‐β1 response throughout the course of osteoblast differentiation. The initiation of a TGF‐β1 effect on cell growth and differentiation is restricted to the proliferative phase of the culture before the cells express the mature osteoblastic phenotype. Second passage cells that are accelerated to differentiate by the addition of dexamethasone or by seeding cultures at a high density are refractory to TGF‐β1. These in vitro results indicate that TGF‐β1 exerts irreversible effects at a specific stage of osteoblast phenotype development resulting in a potent inhibition of osteoblast differentiation at concentrations from 0.1 ng/ml. © 1994 Wiley‐Liss, Inc.

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Authors
Breen, E. C., Ignotz, R. A., McCabe, L., Stein, J. L., Stein, G. S., & Lian, J. B.
Affiliations
University of Massachusetts Chan Medical School (US)
ORCID
Venue
Journal of Cellular Physiology
Publisher
Wiley
Published
1994-08
Volume
160
Issue
2
Pages
323-335
ISSN
  • 0021-9541 (ISSN-L)
  • 1097-4652
DOI
10.1002/jcp.1041600214
OpenAlex
W2070640771
Cited by
138
References
68
Citations by year
2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 3
FWCI
3.80
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3840 d)
Locations
  • Journal of Cellular Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • National Institutes of Health (5r01ar033920-12, 5r01ar035166-09)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR33920, AR 35166, AR 39588, R01AR039588)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
TGF-β1, osteogenic differentiation, osteoblast proliferation, preosteoblasts, extracellular matrix gene expression, fibronectin, osteopontin, type I collagen, alkaline phosphatase, osteocalcin, mineralization, dexamethasone, JunB, c-fos, histones, bone nodules
MeSH terms
Animals, Calcium, Cell Division, Diploidy, Extracellular Matrix, Gene Expression Regulation, Osteoblasts, Osteogenesis, Phenotype, RNA, Messenger, Transforming Growth Factor beta, Proto-Oncogene Proteins c-jun, Proto-Oncogene Proteins c-fos, Rats

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