July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Elevated Bone morphogenic protein 4 (BMP4) Expression implicated in Site-specific Adipogenesis in Thyroid Associated Orbitopathy (TAO)
Author Affiliations & Notes
  • Kam-lung, Kelvin Chong
    Ophthalmology and Visual Science, The Chinese University of Hong Kong, Hong Kong, Hong Kong
    Ophthalmology and Visual Science, Prince of Wales Hospital , Hong Kong, Hong Kong
  • Janice Wong
    Ophthalmology and Visual Science, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • WAI KIT CHU
    Ophthalmology and Visual Science, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • Chi Pui Pang
    Ophthalmology and Visual Science, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • Footnotes
    Commercial Relationships   Kam-lung, Kelvin Chong, None; Janice Wong, None; WAI KIT CHU, None; Chi Pui Pang, None
  • Footnotes
    Support  CUHK direct grant
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1145. doi:
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      Kam-lung, Kelvin Chong, Janice Wong, WAI KIT CHU, Chi Pui Pang; Elevated Bone morphogenic protein 4 (BMP4) Expression implicated in Site-specific Adipogenesis in Thyroid Associated Orbitopathy (TAO). Invest. Ophthalmol. Vis. Sci. 2018;59(9):1145.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose :
Periorbital adipose tissue expansion is a key process in TAO. BMP4 is involved in recruiting mesenchymal stem cells into adipogenic lineage. We compared BMP4 expressions and examine its role in adipogenesis using different donor-matched adipose tissue-derived stromal cells (ADSC) from the same TAO patients.

Methods :
ADSC were generated from periorbital (eyelid, orbital) and subcutaneous (abdominal) adipose tissues of TAO patients. Mesenchymal stem cell (MSC) markers and BMP4 expression were characterized by RT-PCR and immunofluorescent staining. Induced adipogenesis were quantified by mRNA expression of adipogenic markers PPARγ and perilipin measured before and after silencing endogenous BMP4 expression by siRNA and addition of exogenous BMP4 protein.

Results :
ADSC from all depots expressed comparable levels of MSC markers. BMP4 immunohistochemical staining were stronger in periorbital (eyelid and orbital) than subcutaneous adipose tissues. Higher BMP4 mRNA expressions were found in eyelid (4.4–2489 folds) and orbital (6.9–1811 folds) than in subcutaneous ADSC which decreased during induced adipogenesis (p<0.05). After BMP4 knockdown, eyelid and orbital ADSC showed additional 1.4-fold /1.4-fold and 1.2-fold/1.5-fold increase in PPARγ and perilipin expressions upon adipogenic induction, effect of which were reversed by exogenous BMP4 protein.

Conclusions :
Endogenous BMP4 expressions were higher in periorbital ADSC and adipose tissues than subcutaneous counterparts, which decreased during adipogenic induction. Lowering endogenous BMP4 expression by siRNA enhanced adipogenic efficiency in periorbital ADSC, and such effect was reversed by exogenous BMP4 protein. Our findings suggested an unreported role of high BMP4 expression in modulating site-specific adipogenesis in TAO.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

A. BMP4 mRNA expression was significantly higher in uninduced eyelid and orbital ADSC than the subcutaneous ADSC.
B. BMP4 mRNA expression reduced after induced adipogenesis in eyelid and orbital ADSC. Subc: subcutaneous ADSC.

A. BMP4 mRNA expression was significantly higher in uninduced eyelid and orbital ADSC than the subcutaneous ADSC.
B. BMP4 mRNA expression reduced after induced adipogenesis in eyelid and orbital ADSC. Subc: subcutaneous ADSC.

 

C.quantitative PCR of BMP4 7 days after siRNA knockdown.
quantitative PCR of (D) PPARγ and (E) Perilipin showing increased mRNA levels after BMP4 knockdown which decreased after by exogenous BMP4 in adipogenic induced ADSC. mRNA expression were normalized to GAPDH, and compared to the non-targeting siRNA control. DII: Adipogenic cocktail (Dexamethasone, IBMX, insulin)

C.quantitative PCR of BMP4 7 days after siRNA knockdown.
quantitative PCR of (D) PPARγ and (E) Perilipin showing increased mRNA levels after BMP4 knockdown which decreased after by exogenous BMP4 in adipogenic induced ADSC. mRNA expression were normalized to GAPDH, and compared to the non-targeting siRNA control. DII: Adipogenic cocktail (Dexamethasone, IBMX, insulin)

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