@article{522404c13ca34565b47e89a069f4c7c7,
title = "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.",
author = "Huan Liu and Jin He and Rozita Bagheri-Yarmand and Zongwei Li and Rui Liu and Zhiming Wang and Bach, {Duc hiep} and Huang, {Yung hsing} and Pei Lin and Guise, {Theresa A.} and Gagel, {Robert F.} and Jing Yang",
note = "Funding Information: We thank The University of Texas MD Anderson Myeloma Tissue Bank. This research was supported by the National Institutes of Health/National Cancer Institute (R01 awards CA190863 and CA193362, J.Y.), the American Cancer Society (Research Scholar Grant 127337-RSG-15-069-01-TBG, J.Y.), and the Cancer Prevention Research Institute of Texas (Scholar of CPRIT Established Investigator Award RR190108, T.A.G.). Supported also by the NIH/NCI under award number P30CA016672 (Core Labs) and used the Small Animal Imaging Facility, Bone Histomorphometry, and Research Histology Core Laboratory. We would like to thank Sarah Bronson, ELS, Research Medical Library, The University of Texas MD Anderson Cancer Center, who edited the manuscript. Funding Information: We thank The University of Texas MD Anderson Myeloma Tissue Bank. This research was supported by the National Institutes of Health/National Cancer Institute (R01 awards CA190863 and CA193362, J.Y.), the American Cancer Society (Research Scholar Grant 127337-RSG-15-069-01-TBG, J.Y.), and the Cancer Prevention Research Institute of Texas (Scholar of CPRIT Established Investigator Award RR190108, T.A.G.). Supported also by the NIH/NCI under award number P30CA016672 (Core Labs) and used the Small Animal Imaging Facility, Bone Histomorphometry, and Research Histology Core Laboratory. We would like to thank Sarah Bronson, ELS, Research Medical Library, The University of Texas MD Anderson Cancer Center, who edited the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jun,
day = "27",
doi = "10.1038/s41467-022-31356-7",
language = "English (US)",
volume = "13",
journal = "Nat Commun",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}