Unknown

Dataset Information

0

Osteocyte CIITA aggravates osteolytic bone lesions in myeloma.


ABSTRACT: Osteolytic destruction is a hallmark of multiple myeloma, resulting from activation of osteoclast-mediated bone resorption and reduction of osteoblast-mediated bone formation. However, the molecular mechanisms underlying the differentiation and activity of osteoclasts and osteoblasts within a myelomatous microenvironment remain unclear. Here, we demonstrate that the osteocyte-expressed major histocompatibility complex class II transactivator (CIITA) contributes to myeloma-induced bone lesions. CIITA upregulates the secretion of osteolytic cytokines from osteocytes through acetylation at histone 3 lysine 14 in the promoter of TNFSF11 (encoding RANKL) and SOST (encoding sclerostin), leading to enhanced osteoclastogenesis and decreased osteoblastogenesis. In turn, myeloma cell-secreted 2-deoxy-D-ribose, the product of thymidine catalyzed by the function of thymidine phosphorylase, upregulates CIITA expression in osteocytes through the STAT1/IRF1 signaling pathway. Our work thus broadens the understanding of myeloma-induced osteolysis and indicates a potential strategy for disrupting tumor-osteocyte interaction to prevent or treat patients with myeloma bone disease.

SUBMITTER: Liu H 

PROVIDER: S-EPMC9237076 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

2022-04-23 | GSE200987 | GEO
| PRJNA827810 | ENA
| S-EPMC4312883 | biostudies-literature
| S-EPMC8582565 | biostudies-literature
| S-EPMC3381862 | biostudies-other
| S-EPMC5133815 | biostudies-literature
| S-EPMC9479617 | biostudies-literature
| S-EPMC9706590 | biostudies-literature
| S-EPMC10760955 | biostudies-literature
| S-EPMC8345491 | biostudies-literature