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ResearchIn-Press PreviewBone BiologyHematology
Open Access | 10.1172/JCI159527
1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
Find articles by Gai, D. in: JCI | PubMed | Google Scholar
1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
Find articles by Chen, J. in: JCI | PubMed | Google Scholar
1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Stewart, J.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Nookaew, I.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Ashby, C.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Sun, F.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Cheng, Y.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Li, C.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Garg, T.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Schinke, C.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Chen, F.
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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1Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
2Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, United States of America
3Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, United States of America
4Department of Pathology, University of Iowa, Iowa City, United States of America
5Department of Hematology, Xiangya Hospital, Central South University, Changsha, China
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Published July 26, 2022 - More info
Osteolytic bone disease is a hallmark of multiple myeloma (MM). A significant fraction (~20%) of MM patients do not develop osteolytic lesions (OL). 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 bone marrow (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-sequencing identified 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.
View Table S1. Patient serum CST6 and CST3 concentration.
View Table S2. Top expressed genes in each cluster
View Table S3. Marker genes in M0.
View Table S5. Marker genes in M1.
View Table S6. Marker genes in M2.
View Table S4. Marker genes in M4.
View Table S7. Marker genes in M5.
View Table S8. Marker genes in M7.