Professor Colin Farquharson

The Roslin Institute

Research Interests

My research programme is focused on the fundamental/translational mechanisms underpinning bone growth and development with a specific focus on the genetic and endocrine control of skeletal development.  This work is supported by grants from BBSRC, MRC, Medical Research Scotland, Arthritis Research UK and Industry. I have several inter-related research themes and have created novel mouse models and organ culture techniques to address my research questions.

Defining the mechanisms of skeletal biomineralisation has been a long standing interest of mine.  I discovered a bone-specific phosphatase, PHOSPHO1, and together with colleagues at the Sanford Burnham Prebys Medical Discovery Institute, San Diego we substantiated its non-redundant functional role in bone mineralisation; genetic PHOSPHO1 ablation results in hypomineralised, functionally impaired skeletons with bowing of bones and spontaneous fracture.  Co-ablation of alkaline phosphatase produces complete lack of skeletal mineralisation. This work is actively ongoing producing novel insights into the ability of phosphatases to regulate skeletal mineralisation.  In another project, my group has proven a critical role for SOCS2 in regulating epiphyseal chondrocyte and osteoblast responses to growth hormone. SOCS2 suppresses STAT phosphorylation to inhibit linear growth and bone accretion and the absence of SOCS2 protects against bone loss typical of inflammatory bowel disease. These data are consistent with the premise that increased osteoblast SOCS2 expression represents a critical mediator through which pro-inflammatory cytokines inhibit GH signalling and decrease osteoblast function and bone accrual. This work is done in collaboration with colleagues at the University of Glasgow. Other joint studies, funded by the MRC are investigating the bone phenotype of various mouse models of Duchenes Muscular Dystrophy (DMD) and how bone anabolic agents can prevent the osteopenia that is prevalent in this condition.

In collaboration with colleagues at the RVC and the University of Sheffield, we have generated novel pilot data concerning the crucial process of osteocyte formation. These pilot data indicate that matrix mineralisation drives osteocyte formation and E11 expression and that stabilisation of E11 protein (by cysteine protease inhibitors) is essential for the acquisition of the osteocyte morphology. Further work funded by Arthritis Research UK has allowed us to generate bone specific E11 deficient mice and extend these studies to investigate the role of E11 in the aetiology of osteoarthritis.  Another project in the laboratory in collaboration with colleagues at the University of Oxford and Axis-Shield Diagnostics, Dundee and funded by Medical Research Scotland is developing assays to assess the clinical utility of tenascin-C in inflammatory diseases. 

Selected Publications

  • M. Prideaux, N. Loveridge, A. A. Pitsillides, C. Farquharson. 2012. Extracellular Matrix Mineralization Promotes E11/gp38 Glycoprotein Expression and Drives Osteocytic Differentiation. PLoS One Vol: 7. More»
  • Manisha C. Yadav, Ana Maria Sper Simao, Sonoko Narisawa, Carmen Huesa, Marc D. McKee, Colin Farquharson, Jose Luis Millan. 2011. Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: A unified model of the mechanisms of initiation of skeletal calcification. Journal of Bone and Mineral Research Vol: 26 Pages: 286-297. More»
  • C. Pass, V.E. Macrae, C. Huesa, S.F. Ahmed, C. Farquharson. 2012. SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis. Journal of Bone and Mineral Research Vol: 27 Pages: 1055-1066. More»
  • H. C. Owen, S. J. Roberts, S. F. Ahmed, C. Farquharson. 2008. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes. American Journal of Physiology - Endocrinology and Metabolism Vol: 294 Pages: E1023-E1034. More»
  • Vicky MacRae, Megan Davey, Lynn McTeir, Sonoko Narisawa, Manisha C. Yadav, Jose Luis Millan, Colin Farquharson. 2010. Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization during limb development of the chick. Bone Vol: 46 Pages: 1146-55. More»