Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell Fate

被引：328

作者：

Fan, Yi ^{[1
,2
]}

Hanai, Jun-ichi ^{[3
,4
]}

Le, Phuong T. ^{[5
]}

Bi, Ruiye ^{[2
,6
,7
]}

Maridas, David ^{[5
]}

DeMambro, Victoria ^{[5
]}

Figueroa, Carolina A. ^{[5
]}

Kir, Serkan ^{[8
]}

Zhou, Xuedong ^{[2
]}

Mannstadt, Michael ^{[6
,7
]}

Baron, Roland ^{[1
,6
,7
]}

Bronson, Roderick T. ^{[9
]}

Horowitz, Mark C. ^{[10
]}

Wu, Joy Y. ^{[11
]}

Bilezikian, John P. ^{[12
]}

Dempster, David W. ^{[13
]}

Rosen, Clifford J. ^{[5
]}

Lanske, Beate ^{[1
,6
,7
]}

机构：

[1] Harvard Sch Dent Med, Div Bone & Mineral Res, Boston, MA 02115 USA

[2] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China

[3] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA

[4] Harvard Med Sch, Boston, MA 02215 USA

[5] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA

[6] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA

[7] Harvard Med Sch, Dept Med, Boston, MA 02114 USA

[8] Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[9] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02215 USA

[10] Yale Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06510 USA

[11] Stanford Univ, Sch Med, Div Endocrinol, Stanford, CA 94305 USA

[12] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY 10032 USA

[13] Columbia Univ, Dept Pathol, Coll Phys & Surg, New York, NY 10032 USA

来源：

CELL METABOLISM | 2017年 / 25卷 / 03期

关键词：

INHIBITS ADIPOCYTE DIFFERENTIATION; OSTEOBLASTIC CELLS; MINERAL DENSITY; ADIPOSE-TISSUE; STEM-CELLS; PROTEIN; OSTEOPOROSIS; EXPRESSION; RECEPTOR; ADIPOGENESIS;

D O I：

10.1016/j.cmet.2017.01.001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Intermittent PTH administration builds bone mass and prevents fractures, but its mechanism of action is unclear. We genetically deleted the PTH/PTHrP receptor (PTH1R) in mesenchymal stem cells using Prx1Cre and found low bone formation, increased bone resorption, and high bone marrow adipose tissue (BMAT). Bone marrow adipocytes traced to Prx1 and expressed classic adipogenic markers and high receptor activator of nuclear factor kappa B ligand (Rankl) expression. RANKL levels were also elevated in bone marrow supernatant and serum, but undetectable in other adipose depots. By cell sorting, Pref1(+)RANKL(+) marrow progenitors were twice as great in mutant versus control marrow. Intermittent PTH administration to control mice reduced BMAT significantly. A similar finding was noted in male osteoporotic patients. Thus, marrow adipocytes exhibit osteogenic and adipogenic characteristics, are uniquely responsive to PTH, and secrete RANKL. These studies reveal an important mechanism for PTH's therapeutic action through its ability to direct mesenchymal cell fate.

引用

页码：661 / 672

页数：12

共 47 条

[1] Haploinsufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development [J].

Amizuka, N ;

Karaplis, AC ;

Henderson, JE ;

Warshawsky, H ;

Lipman, ML ;

Matsuki, Y ;

Ejiri, S ;

Tanaka, M ;

Izumi, N ;

Ozawa, H ;

Goltzman, D .

DEVELOPMENTAL BIOLOGY, 1996, 175 (01) :166-176

[2] Increased Bone Marrow Fat in Anorexia Nervosa [J].

Bredella, Miriam A. ;

Fazeli, Pouneh K. ;

Miller, Karen K. ;

Misra, Madhusmita ;

Torriani, Martin ;

Thomas, Bijoy J. ;

Ghomi, Reza Hosseini ;

Rosen, Clifford J. ;

Klibanski, Anne .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (06) :2129-2136

[3] Increased Gs Signaling in Osteoblasts Reduces Bone Marrow and Whole-Body Adiposity in Male Mice [J].

Cain, Corey J. ;

Valencia, Joel T. ;

Ho, Samantha ;

Jordan, Kate ;

Mattingly, Aaron ;

Morales, Blanca M. ;

Hsiao, Edward C. .

ENDOCRINOLOGY, 2016, 157 (04) :1481-1494

[4] Activated parathyroid hormone/parathyroid hormone-related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone [J].

Calvi, LM ;

Sims, NA ;

Hunzelman, JL ;

Knight, MC ;

Giovannetti, A ;

Saxton, JM ;

Kronenberg, HM ;

Baron, R ;

Schipani, E .

JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :277-286

[5] Bone Marrow Adipose Tissue Is an Endocrine Organ that Contributes to Increased Circulating Adiponectin during Caloric Restriction [J].

Cawthorn, William P. ;

Scheller, Erica L. ;

Learman, Brian S. ;

Parlee, Sebastian D. ;

Simon, Becky R. ;

Mori, Hiroyuki ;

Ning, Xiaomin ;

Bree, Adam J. ;

Schell, Benjamin ;

Broome, David T. ;

Soliman, Sandra S. ;

DelProposto, Jenifer L. ;

Lumeng, Carey N. ;

Mitra, Aditi ;

Pandit, Sandeep V. ;

Gallagher, Katherine A. ;

Miller, Joshua D. ;

Krishnan, Venkatesh ;

Hui, Susanta K. ;

Bredella, Miriam A. ;

Fazeli, Pouneh K. ;

Klibanski, Anne ;

Horowitz, Mark C. ;

Rosen, Clifford J. ;

MacDougald, Ormond A. .

CELL METABOLISM, 2014, 20 (02) :368-375

[6] PTHrP inhibits adipocyte differentiation by down-regulating PPARγ activity via a MAPK-dependent pathway [J].

Chan, GK ;

Deckelbaum, RA ;

Bolivar, I ;

Goltzman, D ;

Karaplis, AC .

ENDOCRINOLOGY, 2001, 142 (11) :4900-4909

[7] Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T1/2 mesenchymal cells [J].

Chan, GK ;

Miao, DS ;

Deckelbaum, R ;

Bolivar, I ;

Karaplis, A ;

Goltzman, D .

ENDOCRINOLOGY, 2003, 144 (12) :5511-5520

[8]

Chen JQ, 2014, PLOS ONE, V9, DOI [10.1371/journal.pone.0085161, 10.1371/journal.pone.0101277]

[9] Teriparatide for Idiopathic Osteoporosis in Premenopausal Women: A Pilot Study [J].

Cohen, Adi ;

Stein, Emily M. ;

Recker, Robert. R. ;

Lappe, Joan M. ;

Dempster, David W. ;

Zhou, Hua ;

Cremers, Serge ;

McMahon, Donald J. ;

Nickolas, Thomas L. ;

Mueller, Ralph ;

Zwahlen, Alexander ;

Young, Polly ;

Stubby, Julie ;

Shane, Elizabeth .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2013, 98 (05) :1971-1981

[10] Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis:: A paired biopsy study [J].

Dempster, DW ;

Cosman, F ;

Kurland, ES ;

Zhou, H ;

Nieves, J ;

Woelfert, L ;

Shane, E ;

Plavetic, K ;

Müller, R ;

Bilezikian, J ;

Lindsay, R .

JOURNAL OF BONE AND MINERAL RESEARCH, 2001, 16 (10) :1846-1853

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