Projects per year
Paget’s disease of bone (PDB) is a common disease characterized by osteoclast activation that leads to various skeletal complications. Susceptibility to PDB is mediated by a common variant at the optineurin (OPTN) locus, which is associated with reduced levels of mRNA. However, it is unclear how this leads to the development of PDB. Here, we show that OPTN acts as a negative regulator of osteoclast differentiation in vitro and that mice with a loss-of-function mutation in Optn have increased osteoclast activity and bone turnover. Osteoclasts derived from Optn mutant mice have an increase in NF-κB activation and a reduction in interferon beta expression in response to RANKL when compared to wild-type mice. These studies identify OPTN as a regulator of bone resorption and are consistent with a model whereby genetically determined reductions in OPTN expression predispose to PDB by enhancing osteoclast differentiation.
|Publication status||Published - 10 Nov 2015|
FingerprintDive into the research topics of 'Optineurin Negatively Regulates Osteoclast Differentiation by Modulating NFκB and Interferon signaling; implications for Paget’s disease'. Together they form a unique fingerprint.
- 2 Finished
Genetic and enviromental determinants of Pagets Disease
1/08/12 → 31/01/18
Genetic Determinants of susceptibility,severity and clinical outcome in Pagets disease of bone
Ralston, S. & Albagha, O.
1/05/11 → 31/10/12
- Deanery of Molecular, Genetic and Population Health Sciences - Visitor: Default Visitor
Person: Affiliated Independent Researcher