Extracellular fatty acid binding protein (ex-FABP) is a stress protein expressed during chondrocyte and myoblast differentiation

Objective: We have isolated and characterized in our laboratory a lipocalin specifically binding unsaturated long chain fatty acids (Ex-FABP). In deve loping chicken embryo long bones, Ex-FABP first appears at the boundary of the cone of hypertrophic cartilage. 'In vitro' EX-FABP is highly expressed by differentiating hypertrophic chondrocytes. Ex-FABP is expressed also in the forming myotubes both 'in vivo' and 'in vitro'. In cultured chondrocyte s, Ex-FABP expression is strongly induced by treatment with inflammatory ag ents such as the bacterial liposaccharide LPS or interleukin-6. The possibl e mechanism for this induction was investigated. Expression of Ex-FABP was studied in other stress conditions. Design: To investigate a possible mechanism for Ex-FABP induction by LPS or interleukin-6, we have cultured the cells in the presence of either hydrog en peroxide or the NO donor SNAP (S-nitrosil-acetil-D, L-penicillamine), tw o agents known to produce cellular stresses through the activation of speci fic signalling pathways. To investigate Ex-FABP expression in other stress conditions, chondrocytes were cultured for 3 days in the presence of alpha, alpha -dipyridyl, an agent inhibiting prolyl hydroxylase activity and colla gen secretion, Supplement of this agent to the culture medium results in an impairment of collagen secretion and assembly and the consequent altered i nteraction of the cell with the surrounding extracellular matrix. In additi on Ex-FABP expression was studied also in chondrocytes cultured in the abse nce of serum, a stress condition activating cell defence mechanisms. Results: We have excluded that induction of Ex-FABP expression by inflammat ory agents is mediated by oxidative stress or NO production. Ex-FABP expres sion was induced also by changes in the hypertrophic chondrocyte microenvir onment, considered either as extracellular matrix surrounding the cell in c ulture or as nature and concentration of growth factor in the culture mediu m. Conclusions: No definitive data are so far available on the possible role o f Ex-FABP when induced by cellular stresses. The capacity of the protein to specifically bind and transport unsaturated long chain fatty acids suggest s that lipid metabolism and fatty acid utilization by the cells may be invo lved. Based on literature data the NRL/N-GAL (neu-related lipocalin/neutrop hil gelatinase-associated lipocalin) protein was proposed as a possible mam mal counterpart of the chick Ex-FABR We have suggested that Ex-FABP and NRL /NGAL expression in forming bones and muscles is part of a 'physiological' acute phase response. Interestingly the expression of Ex-FABP and NRL/NGAL is also activated in osteoarthritic cartilage and in the case of NRL/N-GAL during neoplastic transformation of chondrogenic lineage cells. (C) 2001 Os teoArthritis Research Society International.