Absence of GDF5 does not interfere with LPS Toll-like receptor signaling.
OBJECTIVE
Growth and differentiation factor 5 (GDF5), member of TGFBeta superfamily, has been implicated in limb development, and is known to play an important role in joint formation. Its absence leads to brachypodism in mice and a number of skeletal malformation syndromes in humans. Recently, an association was shown between osteo-arthritis and a 5' UTR polymorphism in GDF5 gene. In addition, the role of GDF5 may reach beyond the musculoskeletal system. GDF5 appears present in a lipopolysaccharide (LPS) receptor cluster. Absence of GDF5 may limit the response to LPS. This may have consequences for immune responses and macrophage function in general, and for arthritis in particular. Here we compared the sensitivity of Gdf5(Bp-J/Bp-J) mice and wild type (WT) mice to LPS.


METHODS
Peritoneal macrophages from Gdf5(Bp-J/Bp-J) mice and WT mice were stimulated for 18h with LPS (0, 10 or 100 ng/ml). The supernatant was collected and TNF release was measured by ELISA and by an indirect luciferase assay using LNF-luc C3 cells. Gdf5(Bp-J/Bp-J) mice and WT mice were injected with LPS i.p. (30 mg/kg) and LPS induced lethality was checked every 3 hours for 36 hours.


RESULTS
Gdf5(Bp-J/Bp-J) macrophages showed no difference in TNF expression upon LPS stimulation measured by ELISA and by indirect luciferase assay. Gdf5(Bp-J/Bp-J) mice died upon a lethal dose of LPS, as is seen in WT controls.


CONCLUSIONS
Absence of Gdf5 appears not to affect the LPS response. Mice with a reduced expression of Gdf5 can be used in disease models which are dependent on LPS boost.
Daans
M
M
Laboratory for Skeletal Development and Joint Disorders, Division of Rheumatology, Department of Musculoskeletal Sciences, Katholieke Universiteit Leuven, Leuven, Belgium.
Lories
R J U
RJ
Luyten
F P
FP
D000818:Animals; D001168:Arthritis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D055428:Growth Differentiation Factor 5 / Q000235:genetics* / Q000378:metabolism*; D007107:Immune System / Q000378:metabolism / Q000503:physiopathology; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha