Author

Shalini Sethi

Defense Date

6-22-2010

Graduation Date

2010

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Pharmacology

School

School of Pharmacy

Committee Chair

Paula Witt-Enderby

Committee Member

Vicki Davis

Committee Member

Jane Cavanaugh

Committee Member

John Pollock

Committee Member

Rehana Leak

Keywords

Beta-arrestin, Desensitization, Melatonin receptors, Mesenchymal stem cells, Mutations, Osteoblasts

Abstract

Melatonin has been reported to enhance the differentiation of osteoblasts. The purpose of this study was to determine the melatonin treatment that would differentiate human mesenchymal stem cells (hAMSCs) into osteoblasts. A 21 d continuous melatonin treatment significantly increased the alkaline phosphatase (ALP) activity and the deposition of calcium in hAMSCs. These effects were inhibited by MT2 specific antagonist- 4P-PDOT. The time periods of melatonin treatment that increased the expression of osteogenic genes indicated both a sensitized and desensitized receptors with respect to cAMP signaling, signifying two distinct mechanisms of melatonin's action. Unlike the parathyroid hormone which is administered in intermittent doses to increase bone mass, a continuous melatonin treatment may be effective in having an anabolic effect on bone.

Format

PDF

Language

English

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