Osteocyte CIITA aggravates osteolytic bone lesions in myeloma

Huan Liu, Jin He, Rozita Bagheri-Yarmand, Zongwei Li, Rui Liu, Zhiming Wang, Duc hiep Bach, Yung hsing Huang, Pei Lin, Theresa A. Guise, Robert F. Gagel, Jing Yang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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.

Original languageEnglish (US)
Article number3684
Pages (from-to)3684
JournalNature Communications
Issue number1
StatePublished - Jun 27 2022


  • Humans
  • Multiple Myeloma/complications
  • Nuclear Proteins
  • Osteoblasts/metabolism
  • Osteoclasts/metabolism
  • Osteocytes/metabolism
  • Osteolysis/metabolism
  • RANK Ligand/metabolism
  • Trans-Activators
  • Tumor Microenvironment

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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