Citrullination is a calcium-dependent process catalysed by a family of enzymes known as peptidylarginine deiminases (PADIs). PADI type II (PADI2) is strongly linked with the autoimmune disease rheumatoid arthritis, but more recently it has become an attractive research target due to its link with cancer. PADI2 overexpression is found in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) patients. In this report, we aim to determine the nature of citrullinated proteins in bone marrow stromal cells (BMSCs), the effect this has on their function, and the effect of hypoxia on PADI2 expression. Citrullinated proteins were analysed by immunoblot analysis of HS-5 and HEK293T cell lines after addition of either calcium to stimulate PADI2 activity, or EDTA to inhibit it. HS-5 cells were placed into hypoxic conditions (1% oxygen) for up to 32 hours and analysed by an immunoblot to detect changes in PADI2 expression. The data from this study highlights changes in citrullination between calcium and EDTA treated cells in the HS-5 and HEK293T cell lines. Additionally, PADI2 expression is increased in HS-5 cells after two hours, and maintained after six hours in hypoxia, suggesting hypoxic conditions have an impact on PADI2 activity, and therefore, citrullination. In MM, hypoxia is known to have an effect on the malignant plasma cells, allowing them to migrate and home to new areas of the bone marrow (BM). Although in its initial stages, this study has begun to expand our understanding of the effect citrullination has on BMSC function within the BM microenvironment.
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Investigating the tumourigenic aspects of the bone marrow microenvironment in multiple myeloma
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