Inhibition of microRNA-138 enhances bone formation in multiple myeloma bone marrow niche

被引：36

作者：

Tsukamoto, Shokichi ^{[1
]}

Lovendorf, Marianne B. ^{[1
,2
]}

Park, Jihye ^{[1
]}

Salem, Karma Z. ^{[1
]}

Reagan, Michaela R. ^{[1
,3
]}

Manier, Salomon ^{[1
]}

Zavidij, Oksana ^{[1
]}

Rahmat, Mahshid ^{[1
]}

Huynh, Daisy ^{[1
]}

Takagi, Satoshi ^{[1
]}

Kawano, Yawara ^{[1
]}

Kokubun, Katsutoshi ^{[1
]}

Thrue, Charlotte Albaek ^{[2
,4
]}

Nagano, Kenichi ^{[5
]}

Petri, Andreas ^{[2
,4
]}

Roccaro, Aldo M. ^{[1
,6
,7
]}

Capelletti, Marzia ^{[1
]}

Baron, Roland ^{[5
]}

Kauppinen, Sakari ^{[2
,4
]}

Ghobrial, Irene M. ^{[1
]}

机构：

[1] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA

[2] Aalborg Univ Campus Copenhagen, Dept Clin Med, Ctr RNA Med, Copenhagen, Denmark

[3] Maine Med Ctr, Res Inst, Scarborough, ME USA

[4] Aalborg Univ Hosp, Dept Haematol, Aalborg, Denmark

[5] Harvard Med Sch, Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA

[6] ASST Spedali Civili Brescia, Clin Res Dev, Brescia, BS, Italy

[7] ASST Spedali Civili Brescia, Phase Unit 1, Brescia, BS, Italy

来源：

LEUKEMIA | 2018年 / 32卷 / 08期

关键词：

MESENCHYMAL STEM-CELLS; REGULATES OSTEOGENIC DIFFERENTIATION; DOWN-REGULATION; NUCLEIC-ACIDS; UP-REGULATION; CARTILAGE; LNA; INTERLEUKIN-1; CHONDROCYTES; SUPPRESSOR;

D O I：

10.1038/s41375-018-0161-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Myeloma bone disease is a devastating complication of multiple myeloma (MM) and is caused by dysregulation of bone remodeling processes in the bone marrow microenvironment. Previous studies showed that microRNA-138 (miR-138) is a negative regulator of osteogenic differentiation of mesenchymal stromal cells (MSCs) and that inhibiting its function enhances bone formation in vitro. In this study, we explored the role of miR-138 in myeloma bone disease and evaluated the potential of systemically delivered locked nucleic acid (LNA)-modified anti-miR-138 oligonucleotides in suppressing myeloma bone disease. We showed that expression of miR-138 was significantly increased in MSCs from MM patients (MM-MSCs) and myeloma cells compared to those from healthy subjects. Furthermore, inhibition of miR-138 resulted in enhanced osteogenic differentiation of MM-MSCs in vitro and increased the number of endosteal osteoblastic lineage cells (OBCs) and bone formation rate in mouse models of myeloma bone disease. RNA sequencing of the OBCs identified TRPS1 and SULF2 as potential miR-138 targets that were de-repressed in anti-miR-138-treated mice. In summary, these data indicate that inhibition of miR-138 enhances bone formation in MM and that pharmacological inhibition of miR-138 could represent a new therapeutic strategy for treatment of myeloma bone disease.

引用

页码：1739 / 1750

页数：12

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