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- W2331933060 abstract "Multiple myeloma (MM) cells secrete osteoclastogenic factors that promote osteolytic lesions; however, the identity of these factors is largely unknown. Here, we performed a screen of human myeloma cells to identify pro-osteoclastogenic agents that could potentially serve as therapeutic targets for ameliorating MM-associated bone disease. We found that myeloma cells express high levels of the matrix metalloproteinase MMP-13 and determined that MMP-13 directly enhances osteoclast multinucleation and bone-resorptive activity by triggering upregulation of the cell fusogen DC-STAMP. Moreover, this effect was independent of the proteolytic activity of the enzyme. Further, in mouse xenograft models, silencing MMP-13 expression in myeloma cells inhibited the development of osteolytic lesions. In patient cohorts, MMP-13 expression was localized to BM-associated myeloma cells, while elevated MMP-13 serum levels were able to correctly predict the presence of active bone disease. Together, these data demonstrate that MMP-13 is critical for the development of osteolytic lesions in MM and that targeting the MMP-13 protein — rather than its catalytic activity — constitutes a potential approach to mitigating bone disease in affected patients." @default.
- W2331933060 created "2016-06-24" @default.
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- W2331933060 date "2016-04-04" @default.
- W2331933060 modified "2023-10-16" @default.
- W2331933060 title "Multiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease" @default.
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- W2331933060 doi "https://doi.org/10.1172/jci80276" @default.
- W2331933060 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4855918" @default.
- W2331933060 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27043283" @default.
- W2331933060 hasPublicationYear "2016" @default.
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