Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility

被引：109

作者：

Tencerova, Michaela ^{[1
,2
,7
]}

Frost, Morten ^{[1
,2
,3
]}

Figeac, Florence ^{[1
,2
]}

Nielsen, Tina Kamilla ^{[1
,2
]}

Ali, Dalia ^{[1
,2
]}

Lauterlein, Jens-Jacob Lindegaard ^{[1
,2
]}

Andersen, Thomas Levin ^{[4
,5
,6
]}

Haakonsson, Anders Kristian ^{[1
,2
,7
]}

Rauch, Alexander ^{[1
,2
]}

Madsen, Jonna Skov ^{[8
,9
]}

Ejersted, Charlotte ^{[10
]}

Hojlund, Kurt ^{[3
,5
]}

Kassem, Moustapha ^{[1
,2
,11
]}

机构：

[1] Univ Southern Denmark, KMEB, Dept Mol Endocrinol, DK-5000 Odense C, Denmark

[2] Odense Univ Hosp, DK-5000 Odense C, Denmark

[3] Odense Univ Hosp, Steno Diabet Ctr Odense, DK-5000 Odense C, Denmark

[4] Odense Univ Hosp, Dept Pathol, Clin Cell Biol, DK-5000 Odense C, Denmark

[5] Univ Southern Denmark, Dept Clin Res, DK-5000 Odense C, Denmark

[6] Univ Southern Denmark, Dept Mol Med, DK-5000 Odense C, Denmark

[7] Odense Univ Hosp, Odense Patient Data Explorat Network, OPEN, Odense, Denmark

[8] Univ Southern Denmark, Inst Reg Hlth Sci, DK-5000 Odense C, Denmark

[9] Lillebaelt Hosp, Dept Biochem & Immunol, DK-7100 Vejle, Denmark

[10] Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense C, Denmark

[11] Univ Copenhagen, DanStem Danish Stem Cell Ctr, Panum Inst, Dept Cellular & Mol Med, Copenhagen, Denmark

来源：

CELL REPORTS | 2019年 / 27卷 / 07期

关键词：

HIGH-FAT DIET; INSULIN-RESISTANCE; SKELETAL-MUSCLE; ADIPOSE-TISSUE; OSTEOBLAST DIFFERENTIATION; IDENTIFICATION; ADIPOGENESIS; RESTRICTION; INHIBITION; WEIGHT;

D O I：

10.1016/j.celrep.2019.04.066

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Obesity is associated with increased risk for fragility fractures. However, the cellular mechanisms are unknown. Using a translational approach combining RNA sequencing and cellular analyses, we investigated bone marrow stromal stem cells (BM-MSCs) of 54 men divided into lean, overweight, and obese groups on the basis of BMI. Compared with BM-MSCs obtained from lean, obese BM-MSCs exhibited a shift of molecular phenotype toward committed adipocytic progenitors and increased expression of metabolic genes involved in glycolytic and oxidoreductase activity. Interestingly, compared with paired samples of peripheral adipose tissue-derived stromal cells (AT-MSCs), insulin signaling of obese BM-MSCs was enhanced and accompanied by increased abundance of insulin receptor positive (IR+) and leptin receptor positive (LEPR+) cells in BM-MSC cultures. Their hyper-activated metabolic state was accompanied by an accelerated senescence phenotype. Our data provide a plausible explanation for the bone fragility in obesity caused by enhanced insulin signaling leading to accelerated metabolic senescence of BM-MSCs.

引用

页码：2050 / +

页数：19

共 78 条

[1] CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells [J].