Expression of osteoblast and osteoclast regulatory genes in the bone marrow microenvironment in multiple myeloma: only up-regulation of Wnt inhibitors SFRP3 and DKK1 is associated with lytic bone disease

Ida B Kristensen, Jacob Haaber Christensen, Maria B Lyng, Michael B Møller, Lise Pedersen, Lars M Rasmussen, Henrik J Ditzel, Niels Abildgaard

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Multiple myeloma (MM) lytic bone disease (LBD) is caused by osteoclast activation and osteoblast inhibition. RANK/RANKL/OPG play central roles in osteoclast activation and Wnt inhibitor DKK1 in osteoblast inhibition. The role of other Wnt inhibitors is less clear. We evaluated gene expression of osteoclast regulators (RANK, RANKL, OPG, TRAIL, MIP1A), Wnt inhibitors (DKK1, SFRP2, SFRP3, sclerostin, WIF1) and osteoblast transcription factors (RUNX2, osterix) by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the bone marrow (BM) microenvironment using snap-frozen BM biopsies, thereby achieving minimal post-sampling manipulation, and gene expression profiling (GEP) data, reflecting the in vivo situation. We analyzed 110 biopsies from newly diagnosed patients with MM and monoclonal gammopathy of unknown significance (MGUS) and healthy volunteers. LBD was evaluated using standard radiographs and the bone resorption marker CTX-1. Protein levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Among Wnt inhibitors, only SFRP3 and DKK1 were significantly overexpressed in advanced LBD, correlating with protein levels. SFRP3 correlated with CTX-1. Our findings support osteoblast inhibition as the driving force behind MM LBD.

    Original languageEnglish
    Pages (from-to)911-9
    Number of pages9
    JournalLeukemia and Lymphoma
    Volume55
    Issue number4
    DOIs
    Publication statusPublished - Apr 2014

    Keywords

    • Adult
    • Aged
    • Bone Marrow/pathology
    • Computational Biology
    • Female
    • Gene Expression Profiling
    • Gene Expression Regulation, Neoplastic
    • Glycoproteins/genetics
    • Humans
    • Immunohistochemistry
    • Intercellular Signaling Peptides and Proteins/genetics
    • Intracellular Signaling Peptides and Proteins
    • Male
    • Middle Aged
    • Multiple Myeloma/complications
    • Neoplasm Staging
    • Osteoblasts/metabolism
    • Osteoclasts/metabolism
    • Osteolysis/etiology
    • Tumor Microenvironment/genetics

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