Curcuminoids in the Prevention of Osteoclast-Mediated Bone Resorption in Translational Models of Postmenopausal Osteoporosis and Lytic Breast Cancer Bone Metastasis

Persistent Link:
http://hdl.handle.net/10150/222897
Title:
Curcuminoids in the Prevention of Osteoclast-Mediated Bone Resorption in Translational Models of Postmenopausal Osteoporosis and Lytic Breast Cancer Bone Metastasis
Author:
Wright, Laura E.
Issue Date:
2012
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The studies presented in this dissertation offer evidence to support the hypothesis that polyphenolic curcuminoids isolated from the plant turmeric (Curcuma longa L.) are bone-protective in metabolic bone disorders characterized by excessive osteoclastic bone resorption. Activation of the critical transcription factor NF-kappaB in osteoclast precursor RAW 264.7 cells and osteoclastogenesis in rat primary bone marrow cell culture were directly inhibited by curcuminoids. Loss of bone mineral density and impaired structural connectivity of the trabecular bone microarchitecture associated with ovariectomy and estrogen deficiency were attenuated by curcuminoids in a rat model of postmenopausal osteoporosis. Additionally, the studies presented in this dissertation offer evidence for bone-protection conferred by curcuminoids by demonstrating for the first time their potent inhibitory effect on breast cancer cell secretion of the osteolytic peptide parathyroid hormone-related protein (PTHrP) via inhibition of Smad-dependent TGF-beta signaling in MDA-MB-231 cells. Finally, curcuminoids inhibited osteolytic lesion formation in a PTHrP-mediated murine model of breast cancer bone metastasis. Taken together, these novel and encouraging findings justify the need for further studies to determine whether curcuminoids may hold promise for the prevention of bone loss and associated complications in resorptive bone diseases in women.
Type:
text; Electronic Dissertation
Keywords:
Curcuminoids; Metastasis; Osteoclast; Osteoporosis; Physiological Sciences; Bone; Breast Cancer
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Funk, Janet L.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleCurcuminoids in the Prevention of Osteoclast-Mediated Bone Resorption in Translational Models of Postmenopausal Osteoporosis and Lytic Breast Cancer Bone Metastasisen_US
dc.creatorWright, Laura E.en_US
dc.contributor.authorWright, Laura E.en_US
dc.date.issued2012-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe studies presented in this dissertation offer evidence to support the hypothesis that polyphenolic curcuminoids isolated from the plant turmeric (Curcuma longa L.) are bone-protective in metabolic bone disorders characterized by excessive osteoclastic bone resorption. Activation of the critical transcription factor NF-kappaB in osteoclast precursor RAW 264.7 cells and osteoclastogenesis in rat primary bone marrow cell culture were directly inhibited by curcuminoids. Loss of bone mineral density and impaired structural connectivity of the trabecular bone microarchitecture associated with ovariectomy and estrogen deficiency were attenuated by curcuminoids in a rat model of postmenopausal osteoporosis. Additionally, the studies presented in this dissertation offer evidence for bone-protection conferred by curcuminoids by demonstrating for the first time their potent inhibitory effect on breast cancer cell secretion of the osteolytic peptide parathyroid hormone-related protein (PTHrP) via inhibition of Smad-dependent TGF-beta signaling in MDA-MB-231 cells. Finally, curcuminoids inhibited osteolytic lesion formation in a PTHrP-mediated murine model of breast cancer bone metastasis. Taken together, these novel and encouraging findings justify the need for further studies to determine whether curcuminoids may hold promise for the prevention of bone loss and associated complications in resorptive bone diseases in women.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectCurcuminoidsen_US
dc.subjectMetastasisen_US
dc.subjectOsteoclasten_US
dc.subjectOsteoporosisen_US
dc.subjectPhysiological Sciencesen_US
dc.subjectBoneen_US
dc.subjectBreast Canceren_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorFunk, Janet L.en_US
dc.contributor.committeememberGoing, Scott B.en_US
dc.contributor.committeememberHoyer, Patricia B.en_US
dc.contributor.committeememberSchroeder, Joyce A.en_US
dc.contributor.committeememberFunk, Janet L.en_US
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