Unknown

Dataset Information

0

Multiple myeloma-derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease.


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.

SUBMITTER: Fu J 

PROVIDER: S-EPMC4855918 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC9479617 | biostudies-literature
2022-09-21 | GSE191258 | GEO
| S-EPMC6391661 | biostudies-literature
| S-EPMC4537049 | biostudies-literature
| PRJNA791247 | ENA
| S-EPMC5135585 | biostudies-literature
| S-EPMC4312883 | biostudies-literature
| S-EPMC8345491 | biostudies-literature
| S-EPMC5058712 | biostudies-literature
| S-EPMC8582565 | biostudies-literature