Research groups

Research

Cartilage and bone homeostasis in development and disease

Osteoarthritis is a joint condition, characterised by loss of cartilage and increased bone deposition, that affects millions of people worldwide and for which there is currently no pharmaceutical cure. Recent studies have shown that there is a strong genetic component of the disease and that many of the genes and signals implicated in osteoarthritis progression overlap with those involved in normal skeletal development.

19 day old fish expressing GFP under control of the osteocalcin

promoter – this labels the mature osteoblasts and allows

us to follow bone formation in the living fish

We use the zebrafish as a model because it combines excellent genetics with beautiful imaging possibilities, allowing us to study the development of the skeletal system dynamically in vivo. The lab uses an integrated approach based on genetics, cell biology and biochemistry to conduct research on two main projects:

• The mapping and characterisation of a number of mutant genes, identified in a forward genetic screen for phenotypes resembling osteoarthritis (loss of cartilage matrix, increased bone deposition and loss of joint integrity). This will identify novel genes involved in osteoarthritis progression and hopefully new therapeutic targets.
• Studying the role of the cartilage matrix in controlling osteoblast differentiation and cartilage:bone homeostasis.

Craniofacial joints in wild type fish (left)and skeletor mutants (right). In the mutants the cartilage is disorganised and leads to changes to the joint shape and function.

Recent publications

Trpv5/6 is vital for epithelial calcium uptake and bone formation. Vanoevelen J, Janssens A, Huitema LF, Hammond CL, Metz JR, Flik G, Voets T, Schulte-Merker S. FASEB J. 2011 Sep;25(9):3197-207.

Bone regenerates via dedifferentiation of osteoblasts in the zebrafish fin. Knopf F, Hammond C, Chekuru A, Kurth T, Hans S, Weber CW, Mahatma G, Fisher S, Brand M, Schulte-Merker S, Weidinger G. Dev Cell. 2011 May 17;20(5):713-24.

Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Evangelou E, arcOGEN Consortium, Hammond CL, et al. Ann Rheum Dis. 2010 Nov 10. (epub ahead of print).

Two populations of endochondral osteoblasts with differential sensitivity to Hedgehog signaling. Hammond CL and Schulte-Merker S. Development. 2009 Dec;136(23):3991-4000.

In ovo temperature manipulation influences embryonic motility and growth of limb tissues in the chick (Gallus gallus). Hammond CL, Simbi BH, Stickland NC. J Exp Biol. 2007 Aug;210(Pt 15):2667-75.

Signals and myogenic regulatory factors restrict pax3 and pax7 expression to dermomyotome-like tissue in zebrafish. Hammond CL, Hinits Y, Osborn DP, Minchin JE, Tettamanti G, Hughes SM. Dev Biol. 2007 Feb 15;302(2):504-21.

View all publications listed on the University of Bristol's publication database