Fibronectin in in human bone tissue remodelling
The extracellular matrix component fibronectin (fn) has fundamental functions in cell attachment, differentiation, proliferation and in cell migration. Embryonic forms of cellular fn, named EDA-fn and EDB-fn, are generated by alternative splicing. They are detected in proliferating tissue, wound healing and tumor invasion.
This study aimed to quantify fn and its splice variants in the most frequent highly malignant human bone tumor (osteosarcoma) in comparison to bone fracture healing tissue as a model for a physiological bone repair process.
A real-time quantitative RT-PCR assay (Lightcycler System, Roche) was developed to quantify levels of fn, EDA-fn and EDB-fn mRNA. Relative expression was correlated to cell proliferation and differentiation (detected immunohistochemically by Ki67 and CD31 marker) and to the level of osteoid formation.
Both, osteosarcoma and bone fracture healing tissue, did express higher levels of the embryonic fn variants (EDA-fn, EDB-fn) compared to unspliced fn. No significant differences were found in the EDA-fn and EDB-fn mRNA expression comparing tissue remodelling in malignant or physiological repair processes. EDA-fn and EDB-fn expression in osteosarcoma did correlate to the osteoid formation.
In conclusion, embryonic fn splice variants are a strong marker for active granulation and tissue remodelling processes in human bones comparable with wound healing processes. The stimulating effect of fn splice variants on reparative and proliferative processes can be found in physiological bone remodelling as well as in malignant transformation. EDA-fn and EDB-fn mRNA expression levels are a marker for the malignant differentiation in osteosarcoma.