Osteocyte CIITA Aggravates Osteolytic Bone Lesions in Myeloma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA827810 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18794132_1.fastq.gz | Fastqsanger.gz | |||
| SRR18794132_2.fastq.gz | Fastqsanger.gz | |||
| SRR18794133_1.fastq.gz | Fastqsanger.gz | |||
| SRR18794133_2.fastq.gz | Fastqsanger.gz | |||
| SRR18794134_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
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