Publication:
The control of bone formation by neuropeptide Y receptors
The control of bone formation by neuropeptide Y receptors
dc.contributor.author | Alison, Susan Jean | en_US |
dc.date.accessioned | 2022-03-21T12:15:32Z | |
dc.date.available | 2022-03-21T12:15:32Z | |
dc.date.issued | 2006 | en_US |
dc.description.abstract | Osteoporosis is a growing health concern, characterised by deterioration of bone and increased fracture incidence. Anabolic treatments for reversing bone loss are presently limited. A bone anabolic response was recently reported following deletion of hypothalamic neuropeptide Y2 receptors in mice. In contrast, no discernable bone phenotype was observed in Y4 receptor knockout (Y4-/-) mice, revealing specificity between the Y receptors in their control of bone formation. Studies in this thesis revealed a second anabolic response in the absence of another Y receptor subtype; the Y1 receptor. The potential interaction between the Y1 and Y2- anabolic pathways with each other and with Y4 was investigated through the generation of mouse models lacking multiple Y receptor subtypes. Interestingly, no synergistic elevation in bone volume was observed in Y1-/-Y2-/- double knockout mice, indicative of shared mechanisms of action. In contrast, the synergistic elevation in bone volume of male Y2-/- Y4-/- mice was likely due to additive effects of leptin signalling. Consequentially, potential interaction between Y receptors and leptin was investigated by crossing the Y receptor knockouts onto the leptin deficient ob/ob background, revealing differential responses of the Y receptor pathways to leptin deficiency, with the anabolic response of the Y2-/- model retained in Y2-/-/ob mice but abolished in Y1-/-/ob mice compared to Y1-/-. Differential responses of these two pathways were also revealed following gonadectomy of Y1-/- and Y2-/- mice. Importantly, these studies also demonstrated the ability of the central Y2- anabolic pathway to halt gonadectomy-induced bone loss. Interestingly, cultured stromal cells from germline Y2-/- mice exhibited an enhanced ability to undergo mineralisation and adipocyte differentiation, associated with a greater number of mesenchymal progenitor cells present within the bone of Y2-/- mice, suggesting a potential mechanism for the greater mineralisation of the Y2-/- model in vitro and in vivo. Y1 receptor expression was also detected in stromal cells from wild type mice, but was nearly abolished in Y2-/- mice. Together these findings demonstrate an important therapeutic potential for these pathways in the treatment of osteoporosis and indicate that modulation of Y receptor signalling within the bone microenvironment may alter proportions of mesenchymal progenitor populations with effects on bone formation. | en_US |
dc.identifier.uri | http://hdl.handle.net/1959.4/26188 | |
dc.language | English | |
dc.language.iso | EN | en_US |
dc.publisher | UNSW, Sydney | en_US |
dc.rights | CC BY-NC-ND 3.0 | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/au/ | en_US |
dc.subject.other | Bone | en_US |
dc.subject.other | Neuropeptide Y | en_US |
dc.title | The control of bone formation by neuropeptide Y receptors | en_US |
dc.type | Thesis | en_US |
dcterms.accessRights | open access | |
dcterms.rightsHolder | Alison, Susan Jean | |
dspace.entity.type | Publication | en_US |
unsw.accessRights.uri | https://purl.org/coar/access_right/c_abf2 | |
unsw.identifier.doi | https://doi.org/10.26190/unsworks/16057 | |
unsw.relation.faculty | Medicine & Health | |
unsw.relation.originalPublicationAffiliation | Alison, Susan Jean, Garvan Institute of Medical Research, Faculty of Medicine, UNSW | en_US |
unsw.relation.school | Garvan Institute | * |
unsw.thesis.degreetype | PhD Doctorate | en_US |
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