Orbital fibroblasts from thyroid eye disease patients differ in proliferative and adipogenic responses depending on disease subtype

Ajay Kuriyan, Collynn F. Woeller, Charles W. O'Loughlin, Richard P. Phipps, Steven E. Feldon

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose. Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. Methods. Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [3H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied. Results. Type II OFs incorporated 1.7-fold more [3H]thymidine than type I OFs (P <0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P <0.05) and 12.6-fold more lipid than non-TED OFs (P <0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs. Conclusions. We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis.

Original languageEnglish (US)
Pages (from-to)7370-7377
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number12
DOIs
StatePublished - Oct 17 2013

Fingerprint

Eye Diseases
Thyroid Diseases
Fibroblasts
Adipogenesis
Cyclooxygenase Inhibitors
Prostaglandin-Endoperoxide Synthases
Thymidine
Oculomotor Muscles
Flow Cytometry
Staining and Labeling

Keywords

  • Adipogenesis
  • Orbital fibroblasts
  • Proliferation
  • Thyroid eye disease

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Orbital fibroblasts from thyroid eye disease patients differ in proliferative and adipogenic responses depending on disease subtype. / Kuriyan, Ajay; Woeller, Collynn F.; O'Loughlin, Charles W.; Phipps, Richard P.; Feldon, Steven E.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 12, 17.10.2013, p. 7370-7377.

Research output: Contribution to journalArticle

Kuriyan, Ajay ; Woeller, Collynn F. ; O'Loughlin, Charles W. ; Phipps, Richard P. ; Feldon, Steven E. / Orbital fibroblasts from thyroid eye disease patients differ in proliferative and adipogenic responses depending on disease subtype. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 12. pp. 7370-7377.
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abstract = "Purpose. Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. Methods. Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [3H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied. Results. Type II OFs incorporated 1.7-fold more [3H]thymidine than type I OFs (P <0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P <0.05) and 12.6-fold more lipid than non-TED OFs (P <0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs. Conclusions. We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis.",
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T1 - Orbital fibroblasts from thyroid eye disease patients differ in proliferative and adipogenic responses depending on disease subtype

AU - Kuriyan, Ajay

AU - Woeller, Collynn F.

AU - O'Loughlin, Charles W.

AU - Phipps, Richard P.

AU - Feldon, Steven E.

PY - 2013/10/17

Y1 - 2013/10/17

N2 - Purpose. Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. Methods. Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [3H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied. Results. Type II OFs incorporated 1.7-fold more [3H]thymidine than type I OFs (P <0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P <0.05) and 12.6-fold more lipid than non-TED OFs (P <0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs. Conclusions. We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis.

AB - Purpose. Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. Methods. Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [3H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied. Results. Type II OFs incorporated 1.7-fold more [3H]thymidine than type I OFs (P <0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P <0.05) and 12.6-fold more lipid than non-TED OFs (P <0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs. Conclusions. We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis.

KW - Adipogenesis

KW - Orbital fibroblasts

KW - Proliferation

KW - Thyroid eye disease

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