Effects of gonadal and adrenal androgens in a novel androgen-responsive human osteoblastic cell line

Lorenz C. Hofbauer, Kevin C. Hicok, Sundeep Khosla

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

While androgens have important skeletal effects, the mechanism(s) of androgen action on bone remain unclear. Current osteoblast models to study androgen effects have several limitations, including the presence of heterogeneous cell populations. In this study, we examined the effects of androgens on the proliferation and differentiation of a novel human fetal osteoblastic cell line (hFOB/AR-6) that expresses a mature osteoblast phenotype and a physiological number (~4,000/nucleus) of androgen receptors (AR). Treatment with 5α-dihydrotestosterone (5α-DHT) inhibited the proliferation of hFOB/AR-6 cells in a dose-dependent fashion, while it had no effect on the proliferation of hFOB cells, which express low levels of AR (<200/nucleus). In hFOB/AR-6 cells, co-treatment with the specific AR antagonist, hydroxyflutamide abolished 5α-DHT-induced growth inhibition. Steady-state levels of transforming growth factor-β1 (TGF-β1) and TGF- β-induced early gene (TIEG) mRNA decreased after treatment of hFOB/AR-6 cells with 5α-DHT, suggesting a role for the TGF-β1-TIEG pathway in mediating 5α-DHT-induced growth inhibition of hFOB/AR-6 cells. In support of this, co-treatment of hFOB/AR-6 cells with TGF-β1 (40 pg/ml) reversed the 5α-DHT-induced growth inhibition, whereas TGF-β1 alone at this dose had no effect on hFOB/AR-6 cell proliferation. Furthermore, treatment of hFOB/AR-6 cells with 5α-DHT and testosterone (10-8 M) inhibited basal and 1,25- (OH)2D3-induced alkaline phosphatase (ALP) activity and type I collagen synthesis without affecting osteocalcin production. Thus, in this fetal osteoblast cell line expressing a physiological number of AR, androgens decrease proliferation and the expression of markers associated with osteoblast differentiation. These studies suggest that the potential anabolic effect of androgens on bone may not be mediated at the level of the mature osteoblast.

Original languageEnglish (US)
Pages (from-to)96-108
Number of pages13
JournalJournal of Cellular Biochemistry
Volume71
Issue number1
DOIs
StatePublished - Oct 1 1998

Fingerprint

Androgen Receptors
Androgens
Cells
Cell Line
Dihydrotestosterone
Osteoblasts
Transforming Growth Factors
Bone
Growth
Genes
Androgen Receptor Antagonists
Cell Proliferation
Anabolic Agents
Bone and Bones
Osteocalcin
Cell proliferation
Collagen Type I
Alkaline Phosphatase
Testosterone
Phenotype

Keywords

  • Androgen receptor
  • Androgens
  • Antiandrogens
  • Differentiation
  • Osteoblasts
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Effects of gonadal and adrenal androgens in a novel androgen-responsive human osteoblastic cell line. / Hofbauer, Lorenz C.; Hicok, Kevin C.; Khosla, Sundeep.

In: Journal of Cellular Biochemistry, Vol. 71, No. 1, 01.10.1998, p. 96-108.

Research output: Contribution to journalArticle

@article{94082e8bcd254f699e677c5c0dd4d769,
title = "Effects of gonadal and adrenal androgens in a novel androgen-responsive human osteoblastic cell line",
abstract = "While androgens have important skeletal effects, the mechanism(s) of androgen action on bone remain unclear. Current osteoblast models to study androgen effects have several limitations, including the presence of heterogeneous cell populations. In this study, we examined the effects of androgens on the proliferation and differentiation of a novel human fetal osteoblastic cell line (hFOB/AR-6) that expresses a mature osteoblast phenotype and a physiological number (~4,000/nucleus) of androgen receptors (AR). Treatment with 5α-dihydrotestosterone (5α-DHT) inhibited the proliferation of hFOB/AR-6 cells in a dose-dependent fashion, while it had no effect on the proliferation of hFOB cells, which express low levels of AR (<200/nucleus). In hFOB/AR-6 cells, co-treatment with the specific AR antagonist, hydroxyflutamide abolished 5α-DHT-induced growth inhibition. Steady-state levels of transforming growth factor-β1 (TGF-β1) and TGF- β-induced early gene (TIEG) mRNA decreased after treatment of hFOB/AR-6 cells with 5α-DHT, suggesting a role for the TGF-β1-TIEG pathway in mediating 5α-DHT-induced growth inhibition of hFOB/AR-6 cells. In support of this, co-treatment of hFOB/AR-6 cells with TGF-β1 (40 pg/ml) reversed the 5α-DHT-induced growth inhibition, whereas TGF-β1 alone at this dose had no effect on hFOB/AR-6 cell proliferation. Furthermore, treatment of hFOB/AR-6 cells with 5α-DHT and testosterone (10-8 M) inhibited basal and 1,25- (OH)2D3-induced alkaline phosphatase (ALP) activity and type I collagen synthesis without affecting osteocalcin production. Thus, in this fetal osteoblast cell line expressing a physiological number of AR, androgens decrease proliferation and the expression of markers associated with osteoblast differentiation. These studies suggest that the potential anabolic effect of androgens on bone may not be mediated at the level of the mature osteoblast.",
keywords = "Androgen receptor, Androgens, Antiandrogens, Differentiation, Osteoblasts, Proliferation",
author = "Hofbauer, {Lorenz C.} and Hicok, {Kevin C.} and Sundeep Khosla",
year = "1998",
month = "10",
day = "1",
doi = "10.1002/(SICI)1097-4644(19981001)71:1<96::AID-JCB10>3.0.CO;2-G",
language = "English (US)",
volume = "71",
pages = "96--108",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Effects of gonadal and adrenal androgens in a novel androgen-responsive human osteoblastic cell line

AU - Hofbauer, Lorenz C.

AU - Hicok, Kevin C.

AU - Khosla, Sundeep

PY - 1998/10/1

Y1 - 1998/10/1

N2 - While androgens have important skeletal effects, the mechanism(s) of androgen action on bone remain unclear. Current osteoblast models to study androgen effects have several limitations, including the presence of heterogeneous cell populations. In this study, we examined the effects of androgens on the proliferation and differentiation of a novel human fetal osteoblastic cell line (hFOB/AR-6) that expresses a mature osteoblast phenotype and a physiological number (~4,000/nucleus) of androgen receptors (AR). Treatment with 5α-dihydrotestosterone (5α-DHT) inhibited the proliferation of hFOB/AR-6 cells in a dose-dependent fashion, while it had no effect on the proliferation of hFOB cells, which express low levels of AR (<200/nucleus). In hFOB/AR-6 cells, co-treatment with the specific AR antagonist, hydroxyflutamide abolished 5α-DHT-induced growth inhibition. Steady-state levels of transforming growth factor-β1 (TGF-β1) and TGF- β-induced early gene (TIEG) mRNA decreased after treatment of hFOB/AR-6 cells with 5α-DHT, suggesting a role for the TGF-β1-TIEG pathway in mediating 5α-DHT-induced growth inhibition of hFOB/AR-6 cells. In support of this, co-treatment of hFOB/AR-6 cells with TGF-β1 (40 pg/ml) reversed the 5α-DHT-induced growth inhibition, whereas TGF-β1 alone at this dose had no effect on hFOB/AR-6 cell proliferation. Furthermore, treatment of hFOB/AR-6 cells with 5α-DHT and testosterone (10-8 M) inhibited basal and 1,25- (OH)2D3-induced alkaline phosphatase (ALP) activity and type I collagen synthesis without affecting osteocalcin production. Thus, in this fetal osteoblast cell line expressing a physiological number of AR, androgens decrease proliferation and the expression of markers associated with osteoblast differentiation. These studies suggest that the potential anabolic effect of androgens on bone may not be mediated at the level of the mature osteoblast.

AB - While androgens have important skeletal effects, the mechanism(s) of androgen action on bone remain unclear. Current osteoblast models to study androgen effects have several limitations, including the presence of heterogeneous cell populations. In this study, we examined the effects of androgens on the proliferation and differentiation of a novel human fetal osteoblastic cell line (hFOB/AR-6) that expresses a mature osteoblast phenotype and a physiological number (~4,000/nucleus) of androgen receptors (AR). Treatment with 5α-dihydrotestosterone (5α-DHT) inhibited the proliferation of hFOB/AR-6 cells in a dose-dependent fashion, while it had no effect on the proliferation of hFOB cells, which express low levels of AR (<200/nucleus). In hFOB/AR-6 cells, co-treatment with the specific AR antagonist, hydroxyflutamide abolished 5α-DHT-induced growth inhibition. Steady-state levels of transforming growth factor-β1 (TGF-β1) and TGF- β-induced early gene (TIEG) mRNA decreased after treatment of hFOB/AR-6 cells with 5α-DHT, suggesting a role for the TGF-β1-TIEG pathway in mediating 5α-DHT-induced growth inhibition of hFOB/AR-6 cells. In support of this, co-treatment of hFOB/AR-6 cells with TGF-β1 (40 pg/ml) reversed the 5α-DHT-induced growth inhibition, whereas TGF-β1 alone at this dose had no effect on hFOB/AR-6 cell proliferation. Furthermore, treatment of hFOB/AR-6 cells with 5α-DHT and testosterone (10-8 M) inhibited basal and 1,25- (OH)2D3-induced alkaline phosphatase (ALP) activity and type I collagen synthesis without affecting osteocalcin production. Thus, in this fetal osteoblast cell line expressing a physiological number of AR, androgens decrease proliferation and the expression of markers associated with osteoblast differentiation. These studies suggest that the potential anabolic effect of androgens on bone may not be mediated at the level of the mature osteoblast.

KW - Androgen receptor

KW - Androgens

KW - Antiandrogens

KW - Differentiation

KW - Osteoblasts

KW - Proliferation

UR - http://www.scopus.com/inward/record.url?scp=0032189236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032189236&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-4644(19981001)71:1<96::AID-JCB10>3.0.CO;2-G

DO - 10.1002/(SICI)1097-4644(19981001)71:1<96::AID-JCB10>3.0.CO;2-G

M3 - Article

C2 - 9736458

AN - SCOPUS:0032189236

VL - 71

SP - 96

EP - 108

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 1

ER -