ArticleThe Journal of clinical investigation2022
CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Rho-related GTP-binding protein RhoE (RND3) regulates multiple myeloma bone disease.Cancer cell international · 2026Article
- Research on the role and mechanisms of Cystatin 6 in disease pathosis and development.Frontiers in molecular biosciences · 2026Review
- LY6E as a new prognostic biomarker of multiple myeloma-related bone disease.Scientific reports · 2025Article
- Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.Journal of translational medicine · 2025Article
- Article
- Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in multiple myeloma.Communications biology · 2024Article
- Single-cell sequencing analysis of multiple myeloma heterogeneity and identification of new theranostic targets.Cell death & disease · 2024Article
- Cystatin M/E ameliorates bone resorption through increasing osteoclastic cell estrogen influx.Research square · 2024Article
- Restrained Mitf-associated autophagy by Mulberroside A ameliorates osteoclastogenesis and counteracts OVX-Induced osteoporosis in mice.Cell death discovery · 2024Article
- Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth.Nature communications · 2024Article
- BCMA- and CST6-specific CAR T cells lyse multiple myeloma cells and suppress murine osteolytic lesions.The Journal of clinical investigation · 2024Article
- Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression.Cancers · 2023Review
- High NEK2 expression in myeloid progenitors suppresses T cell immunity in multiple myeloma.Cell reports. Medicine · 2023Article
- IL5RA as an immunogenic cell death-related predictor in progression and therapeutic response of multiple myeloma.Scientific reports · 2023Article
- Acute Myeloid Leukemia Causes Serious and Partially Irreversible Changes in Secretomes of Bone Marrow Multipotent Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Article
- Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis.Frontiers in immunology · 2023Review
- Article
- Inhibition of CX3CL1 by treadmill training prevents osteoclast-induced fibrocartilage complex resorption during TBI healing.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
Abstract
Osteolytic bone disease is a hallmark of multiple myeloma (MM). A significant fraction (~20%) of MM patients do not develop osteolytic lesions (OLs). The molecular basis for the absence of bone disease in MM is not understood. We combined PET-CT and gene expression profiling (GEP) of purified BM CD138+ MM cells from 512 newly diagnosed MM patients to reveal that elevated expression of cystatin M/E (CST6) was significantly associated with the absence of OL in MM. An enzyme-linked immunosorbent assay revealed a strong correlation between CST6 levels in BM serum/plasma and CST6 mRNA expression. Both recombinant CST6 protein and BM serum from patients with high CST6 significantly inhibited the activity of the osteoclast-specific protease cathepsin K and blocked osteoclast differentiation and function. Recombinant CST6 inhibited bone destruction in ex vivo and in vivo myeloma models. Single-cell RNA-Seq showed that CST6 attenuates polarization of monocytes to osteoclast precursors. Furthermore, CST6 protein blocks osteoclast differentiation by suppressing cathepsin-mediated cleavage of NF-κB/p100 and TRAF3 following RANKL stimulation. Secretion by MM cells of CST6, an inhibitor of osteoclast differentiation and function, suppresses osteolytic bone disease in MM and probably other diseases associated with osteoclast-mediated bone loss.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.