Replication of fibroblast growth factor and heparan sulphate signalling by thyroid hormone during bone development
Lead Research Organisation:
Imperial College London
Department Name: Unlisted
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
- Imperial College London, United Kingdom (Collaboration, Fellow, Lead Research Organisation)
- Queen Mary, University of London, United Kingdom (Collaboration)
- National Cancer Institute (NCI) (Collaboration)
- University College London, United Kingdom (Collaboration)
- Academic Medical Center (Collaboration)
- Dartmouth College, United States (Collaboration)
- University of Chicago, United States (Collaboration)
- University of Lyon (Collaboration)
- Medical Research Council (Collaboration)
- École normale supérieure de Lyon (ENS Lyon) (Collaboration)
Publications
Barnard JC
(2005)
Thyroid hormones regulate fibroblast growth factor receptor signaling during chondrogenesis.
in Endocrinology
Bassett JH
(2003)
The molecular actions of thyroid hormone in bone.
in Trends in endocrinology and metabolism: TEM
Bassett JH
(2008)
A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism.
in Molecular endocrinology (Baltimore, Md.)
Bassett JH
(2003)
Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions.
in Molecular and cellular endocrinology
Bassett JH
(2007)
Thyroid status during skeletal development determines adult bone structure and mineralization.
in Molecular endocrinology (Baltimore, Md.)
Bassett JH
(2016)
Role of Thyroid Hormones in Skeletal Development and Bone Maintenance.
in Endocrine reviews
Bassett JH
(2007)
Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism.
in Molecular endocrinology (Baltimore, Md.)
Bassett JH
(2006)
Thyroid hormone regulates heparan sulfate proteoglycan expression in the growth plate.
in Endocrinology
Bassett JH
(2008)
Critical role of the hypothalamic-pituitary-thyroid axis in bone.
in Bone
Bassett JH
(2006)
Analysis of skeletal phenotypes in thyroid hormone receptor mutant mice.
in Scanning
| Description | TSH supression in thyroid cancer patients |
| Geographic Reach | Europe |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | TSH suppression is not detrimental in man and premenopausal women but may be detrimental in postmenopausal women. Highlighting importance of osteoporosis surveillance in post menopausal women treated for differentiated thyroid cancer. |
| Description | ARC Equipment Grant |
| Amount | £35,000 (GBP) |
| Organisation | Versus Arthritis |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2008 |
| End | 12/2008 |
| Description | BBSRC Research Grant (F021704/1) |
| Amount | £596,299 (GBP) |
| Funding ID | BB/F021704/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2009 |
| End | 04/2012 |
| Description | BTF Research Grant |
| Amount | £10,000 (GBP) |
| Organisation | British Thyroid Foundation (BTF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2004 |
| End | 01/2006 |
| Description | BTF Research Grant |
| Amount | £10,000 (GBP) |
| Organisation | British Thyroid Foundation (BTF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2007 |
| End | 12/2007 |
| Description | Hammersmith Hospitals Trustees' Equipment Grant |
| Amount | £20,000 (GBP) |
| Organisation | Imperial College Healthcare NHS Trust |
| Sector | Hospitals |
| Country | United Kingdom |
| Start | 01/2007 |
| End | 12/2007 |
| Description | Hammersmith Hospitals Trustees' Research Grant |
| Amount | £10,000 (GBP) |
| Organisation | Imperial College Healthcare NHS Trust |
| Sector | Hospitals |
| Country | United Kingdom |
| Start | 01/2004 |
| End | 12/2006 |
| Description | MRC Project Grant |
| Amount | £498,507 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2009 |
| End | 03/2013 |
| Description | Sir Jules Thorn Trust PhD Studentship |
| Amount | £75,000 (GBP) |
| Organisation | Sir Jules Thorn Charitable Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2008 |
| End | 09/2011 |
| Description | Wellcome Trust Project Grant (GR076584) |
| Amount | £326,126 (GBP) |
| Funding ID | GR076584 |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2006 |
| End | 05/2008 |
| Title | Model of cell type specific hypothyroidism |
| Description | We have generated floxed-Dio3 mice (pROSA26PA/rD3) that over-express the type 3 deiodinase enzyme, which inactivates thyroid hormones, following excision of the floxed cassette |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Provided To Others? | No |
| Impact | We have obtained chondrocyte- (type II collagen-Cre (Col2-cre)), osteoblast- (osteocalcin-Cre(OC-cre)) and osteoclast- (M lysozyme-cre (LysM-cre)) specific Cre mice Thus, we now have the reagents to characterize the role of unliganded thyroid hormone receptors in the 3 bone cell types chondrocytes, osteoblasts and osteoclasts. Furthermore this model system can be used to investigate the role of hypothyroidism in the development of other key thyroid hormore responsive tissues such as the brain. |
| Title | Quantitative Faxitron analysis of the skeleton |
| Description | We purchased a Faxitron MX20 Digital X-ray unit and have developed a novel and rapid method to determine skeletal morphometric parameters and bone mineral content at a resolution of 10 micron. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2008 |
| Provided To Others? | Yes |
| Impact | We have already used this method in a number of in vivo models of skeletal disease generated by other groups. Furthermore, we are currenty performing a pilot project with the Sanger Institute screening 100 consecutive lines, from the Knockout Mouse Project , for skeletal abnormalities. This new methodology was presented at the European Calcified Tissue Society Osteoclast Workshop, Aberdeen in 2008 and as a result we contributed a chapter on quantitative Faxitron analysis to the second addition of "Bone Research Protocols" (Humana Press). |
| Title | Skeletal mechanical testing |
| Description | We purchased an Instron 5543 load frame and have developed bespoke fittings to facilitate 3 point bending, compression and torsional analysis of specimens from in vivo models of skeletal disease. We have also designed custom software to calculate standard material strength parameters in these samples. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | Development of this new methodology has facilitated collaboration with the Kennedy Institute of Rheumatology and the detailed analysis of multiple in vivo models of fracture healing. Furthermore, we are using this methodology in a pilot project with the Sanger Institute screening 100 consecutive lines, from the Knockout Mouse Project. |
| Description | Anita Boelen: Role of the type 3 deiodinase in macrophage activity |
| Organisation | Academic Medical Center |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | Generation of the Rosa26/D3 mouse line and cross with LysM-Cre (monocyte/macrophage lineage specific) |
| Collaborator Contribution | Established S. pneumoniae infection protocol |
| Impact | Experiments in progress |
| Start Year | 2011 |
| Description | Bone phenotype in mice with severe dominant negative mutations of thyroid hormone receptor alpha and beta |
| Organisation | National Cancer Institute (NCI) |
| Country | United States |
| Sector | Public |
| PI Contribution | We have characterised the skeletal phenotypes in these mice during developing (PMID: 17488972 ). We are currently characterizing the severe adult skeletal phenotype in these mice. |
| Collaborator Contribution | Generation of thyroid hormone receptor knockin mice harbouring a severe dominant negative mutations of either thyroid hormone receptor alpha (TRaPV/+) or thyroid hormone receptor beta (TRb(PV/PV). The have provided skeletal samples from these mice. |
| Impact | Publications PMID: 16051666, PMID: 16150908, PMID: 19584945, PMID: 16862217 |
| Description | David Carling Role of type 3 deiodinase in hepatocytes |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Clinical Sciences Centre (CSC) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Generation of Rosa26/D3 mice. These mice were crossed with Alb-Cre mice to generate mice that express the type 3 deiodinase ion hepatocytes. Analysis of phenotype. |
| Collaborator Contribution | Alb-Cre mice and analysis of metabolic phjenotype |
| Impact | In progress |
| Start Year | 2011 |
| Description | Development of high resolution skeletal imaging in mice |
| Organisation | Queen Mary University of London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In collaboration we have analysed the skeletal phenotype of a number genetically modified mice. |
| Collaborator Contribution | Back-scattered electron scanning electron microscopy and confocal microscopy. Continued collaboration has been vital in the skelatal phenotyping of genetically modified mice.Development of key statistical analysis software used in quantitative back-scattered electron scanning electron microscopy |
| Impact | Development of quantitative digital Faxitron analysis and in performing back-scattered electron microscopy. Co-aurthors on the following publications. PMID: 17932107 PMID: 17488972 PMID: 17327419 PMID: 19584945, PMID: 20368437 |
| Description | Development of high resolution skeletal imaging in mice |
| Organisation | University College London |
| Department | Eastman Dental Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In collaboration we have analysed the skeletal phenotype of a number genetically modified mice. |
| Collaborator Contribution | Back-scattered electron scanning electron microscopy and confocal microscopy. Continued collaboration has been vital in the skelatal phenotyping of genetically modified mice.Development of key statistical analysis software used in quantitative back-scattered electron scanning electron microscopy |
| Impact | Development of quantitative digital Faxitron analysis and in performing back-scattered electron microscopy. Co-aurthors on the following publications. PMID: 17932107 PMID: 17488972 PMID: 17327419 PMID: 19584945, PMID: 20368437 |
| Description | Intrauterine transplantation of human fetal mesenchymal stem cells reduces fractures in osteogenesis imperfecta mice |
| Organisation | Imperial College London |
| Department | Institute of Reproductive and Developmental Biology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have assisted in the skeletal phenotyping of these mice. |
| Collaborator Contribution | Developed a murine model for treatement of osteogenesis imperfecta by intrauterine stem cell transplantation. |
| Impact | Initial studies have been published (PMID: 17967940) and PMID: 21088133 |
| Start Year | 2007 |
| Description | Role of Deiodinase enzymes in the skeleton |
| Organisation | Dartmouth College |
| Department | Geisel School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We have characterised the skeletal phenotypes of mice lacking the type 2 deiodinase and mice lacking both the Type 1 and type 2 deiodinase. |
| Collaborator Contribution | Generation of Deiodinase 1, 2 and 3 knockout mice. Skeletal samples from D2KO and D1/D2KO mice have been provided. |
| Impact | Manuscript: "Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts" Proc Natl Acad Sci U S A. 2010 107(16):7604-9 PMID: 20368437 |
| Description | Role of natural killer T cells in the regulation of bone turnover |
| Organisation | Imperial College London |
| Department | Centre for Haematology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have contributed to the design of this study and performed the skeletal analysis. |
| Collaborator Contribution | Investigation of the role of invariant natural killer T (iNKT) cells in adult bone remodelling by analysing mice deficient in iNKT cells. |
| Impact | Revised manuscript submitted to Journal of Imunology "Invariant NKT cells regulate osteoclast development and function" |
| Start Year | 2006 |
| Description | Role of thyroid stimulating hormone in bone |
| Organisation | University of Chicago |
| Department | J. P. Kennedy Mental Retardation and Developmental Disabilities Center |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We characterised the skeletal phenotype in 2 different congenitally hypothyroid mice. Pax8-/- have no thyroid tissue, a 2000 fold elevation of thyroid stimulating hormone (TSH) and a functional TSH receptor. hyt/hyt mice have a severly hypoplastic thyroid, a 2000 fold elevation of TSH but no functional TSH receptor. As a consequence we were able to demostrated that TSH does not have an important role in bone. |
| Collaborator Contribution | Provision of hyt/hyt mice that lack functional TSH receptors. Assistance in the design of experiments that address the role of TSH in bone.Provision of Pax8 knockout mice for this study |
| Impact | This study is published PMID: 17932107 |
| Description | Role of thyroid stimulating hormone in bone |
| Organisation | University of Lyon |
| Department | Institute of Functional Genomics |
| Country | France |
| Sector | Academic/University |
| PI Contribution | We characterised the skeletal phenotype in 2 different congenitally hypothyroid mice. Pax8-/- have no thyroid tissue, a 2000 fold elevation of thyroid stimulating hormone (TSH) and a functional TSH receptor. hyt/hyt mice have a severly hypoplastic thyroid, a 2000 fold elevation of TSH but no functional TSH receptor. As a consequence we were able to demostrated that TSH does not have an important role in bone. |
| Collaborator Contribution | Provision of hyt/hyt mice that lack functional TSH receptors. Assistance in the design of experiments that address the role of TSH in bone.Provision of Pax8 knockout mice for this study |
| Impact | This study is published PMID: 17932107 |
| Description | Skeletal analysis of mice lacking thyroid hormone receptor alpha or beta |
| Organisation | École normale supérieure de Lyon (ENS Lyon) |
| Department | Laboratory of Molecular and Cellular Biology (UMR 5665 CNRS) |
| Country | France |
| Sector | Academic/University |
| PI Contribution | We characterised the skeletal development and adult bone in TRa0/0 and TRb-/- mice and also determined heparan sulphate proteoglycan expression the growth plate in these mice. |
| Collaborator Contribution | Generation of mice lacking all isoforms of either thyroid hormone receptor alpha (TRa0/0) or thyroid hormone receptor beta (TRb-/-). They have provided skeletal samples from these mice. |
| Impact | Results of this collaboration are published in PMID: 17327419 PMID: 17327419 |
| Description | Association of multiple endocrine neoplasia dissorders (AMEND) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Session Chair and symposium speaker on current guidlines for management and treatment of familial thyroid disease. Improved patient education |
| Year(s) Of Engagement Activity | 2009 |
| Description | British Thyroid Foundation Newsletter 2006 |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Report of research outcomes for studies funded by the British Thyroid Foundation Research Award 2004 Highlighted the importance of thyroid research to patient groups. |
| Year(s) Of Engagement Activity | 2006 |
| Description | British Thyroid Foundation Newsletter 2008 |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Participants in your research and patient groups |
| Results and Impact | Report of research outcomes for studies funded by the British Thyroid Foundation Research Award 2007 Highlighted the importance of skeletal thyroid research to patients with thyroid disease. |
| Year(s) Of Engagement Activity | 2008 |
| Description | Careers in Academic Medicine, Royal College of Physicians, London |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | 30 minute lecture entitled "Title: "Why undertake a cereer in Academic medicine: A personal experience" The aim opf this meeting was to increase recruitment of junior doctors into academic medicine |
| Year(s) Of Engagement Activity | 2006 |
| Description | Kings College School Wimbledon |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Meeting for prospective medical and veterinary students from Kings College Wimbledon and their parents to advice regarding university applications and future career possibilities in clinical medicine and academia Opportunity to meet candidates prior to university interview for additional advice |
| Year(s) Of Engagement Activity | 2015 |
| URL | https://www.kcs.org.uk/ |
| Description | School Visit |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Meeting of >50 school children interested in a career in Medicine and Science meeting with physicians and scientists which resulted in discussions about opportunities for studying and pursuing a scientific research career in basic and clinical areas. |
| Year(s) Of Engagement Activity | 2015,2016 |
| URL | https://www.kcs.org.uk/content/science-medics-networking |
| Description | Society for Endocrinology Task Force on Recruitment into Academic Endocrinology |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | This committee advised the Society for Endocinology Executive Committee on mechanisms to improve academic recruitment to the speciality Increased awarness of the speciality as a result of research awards and travel grants. |
| Year(s) Of Engagement Activity | 2008 |