Our laboratory has defined a rapid cellular response in porcine articular cartilage to injury. To
enable study of the injury response in genetically modified animals I have characterized a
novel model of cartilage injury in the mouse, involving avulsion of femoral head epiphyseal
cartilage from 4-6 week old animals, and maintaining the explanted tissue in culture.
Avulsion injury (explantation) of murine cartilage rapidly activated mitogen activated protein
kinases (MAPKs) and nuclear factor κB (NFκB), thus establishing a close similarity to
porcine tissue.
Gene expression (mRNA) was analysed on Taqman® Low density array microfluidic cards
for 47 pre-selected genes. 25 were upregulated upon injury; many characteristic of the
inflammatory response. Some were upregulated early (by 1 h) and some not till after 4 h,
suggesting primary and secondary responses.
Re-cutting cartilage adapted to culture only activated a subset of genes, probably due to
release of fibroblast growth factor 2 (FGF2) which is stored pericellularly. Gene expression
profiling of explanted cartilage of Fgf2-deficient mice showed 7 of the 25 (28%) genes were
partly or largely FGF2-dependent.
Because the gene and signalling profiles resembled an inflammatory response I examined
tissue deficient in the myeloid differentiation 88 protein (MyD88) an adaptor protein for
signalling of the interleukin-1 receptor and toll-like receptor family. 12 of the 25 genes were
MyD88-dependent.
MyD88-/- cartilage did not show impairment of the intracellular signalling response upon
injury and expression of a MyD88-dependent gene (Ccl2) did not increase till 4 h of culture.
It was likely that a MyD88-using ligand was made during the primary response and
contributed to the secondary.
I conclude there are at least 3 mechanisms by which cartilage injury activates gene
expression: 1) release of pericellular FGF2, 2) an unkown trigger of MAPK and NFκB and 3)
secondary production of a MyD88-using factor.