Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

被引：142

作者：

Dole, Neha S. ^{[1
]}

Mazur, Courtney M. ^{[1
,2
]}

Acevedo, Claire ^{[1
,3
]}

Lopez, Justin P. ^{[1
,2
]}

Monteiro, David A. ^{[1
,2
]}

Fowler, Tristan W. ^{[1
]}

Gludovatz, Bernd ^{[3
]}

Walsh, Flynn ^{[3
]}

Regan, Jenna N. ^{[4
]}

Messina, Sara ^{[3
,5
]}

Evans, Daniel S. ^{[6
]}

Lang, Thomas F. ^{[7
]}

Zhang, Bin ^{[8
]}

Ritchie, Robert O. ^{[3
,5
]}

Mohammad, Khalid S. ^{[4
]}

Alliston, Tamara ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA

[2] UC Berkeley UCSF Grad Program Bioengn, San Francisco, CA 94143 USA

[3] Lawrence Berkeley Natl Lab, Mat Sci Div, Berkeley, CA 94720 USA

[4] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA

[5] Univ Calif Berkeley, Dept Mat Sci & Engn, Berkeley, CA 94720 USA

[6] Calif Pacific Med Ctr Res Inst, San Francisco, CA 94107 USA

[7] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA

[8] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA

来源：

CELL REPORTS | 2017年 / 21卷 / 09期

基金：

瑞士国家科学基金会; 美国国家科学基金会;

关键词：

GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; MECHANICAL-PROPERTIES; MINERAL DENSITY; CORTICAL BONE; EXPRESSION; FRACTURE; PERILACUNAR; OSTEOBLASTS; WOMEN;

D O I：

10.1016/j.celrep.2017.10.115

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-beta) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar canalicular matrix led us to hypothesize that TGF-beta controls bone quality through perilacunar canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-beta signaling (TbRIIocy-/-), we show that TGF-beta regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

引用

页码：2585 / 2596

页数：12

共 51 条

[1]

Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures [J].

Ahmed, L. A. ;

Shigdel, R. ;

Joakimsen, R. M. ;

Eldevik, O. P. ;

Eriksen, E. F. ;

Ghasem-Zadeh, A. ;

Bala, Y. ;

Zebaze, R. ;

Seeman, E. ;

Bjornerem, A. .

OSTEOPOROSIS INTERNATIONAL, 2015, 26 (08) :2137-2146

[2]

Biological Regulation of Bone Quality [J].

Alliston, Tamara .

CURRENT OSTEOPOROSIS REPORTS, 2014, 12 (03) :366-375

[3]

TGF-β regulates the mechanical properties and composition of bone matrix [J].

Balooch, G ;

Balooch, M ;

Nalla, RK ;

Schilling, S ;

Filvaroff, EH ;

Marshall, GW ;

Marshall, SJ ;

Ritchie, RO ;

Derynck, R ;

Alliston, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (52) :18813-18818

[4]

The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis [J].

Borton, AJ ;

Frederick, JP ;

Datto, MB ;

Wang, XF ;

Weinstein, RS .

JOURNAL OF BONE AND MINERAL RESEARCH, 2001, 16 (10) :1754-1764

[5]

Tissue-specific calibration of extracellular matrix material properties by transforming growth factor-β and Runx2 in bone is required for hearing [J].

Chang, Jolie L. ;

Brauer, Delia S. ;

Johnson, Jacob ;

Chen, Carol G. ;

Akil, Omar ;

Balooch, Guive ;

Humphrey, Mary Beth ;

Chin, Emily N. ;

Porter, Alexandra E. ;

Butcher, Kristin ;

Ritchie, Robert O. ;

Schneider, Richard A. ;

Lalwani, Anil ;

Derynck, Rik ;

Marshall, Grayson W. ;

Marshall, Sally J. ;

Lustig, Lawrence ;

Alliston, Tamara .

EMBO REPORTS, 2010, 11 (10) :765-771

[6]

Antiresorptive therapies for osteoporosis: a clinical overview [J].

Chen, Jian Sheng ;

Sambrook, Philip N. .

NATURE REVIEWS ENDOCRINOLOGY, 2012, 8 (02) :81-91

[7]

Dallas SL, 2008, PRINCIPLES OF BONE BIOLOGY, VOL 2, 3RD EDITION, P1145, DOI 10.1016/B978-0-12-373884-4.00067-7

[8]

Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy [J].

Delmas, PD ;

Seeman, E .

BONE, 2004, 34 (04) :599-604

[9]

Inhibition of TGF-β Signaling by 1D11 Antibody Treatment Increases Bone Mass and Quality In Vivo [J].

Edwards, James R. ;

Nyman, Jeffry S. ;

Lwin, Seint T. ;

Moore, Megan M. ;

Esparza, Javier ;

O'Quinn, Elizabeth C. ;

Hart, Andrew J. ;

Biswas, Swati ;

Patil, Chetan A. ;

Lonning, Scott ;

Mahadevan-Jansen, Anita ;

Mundy, Gregory R. .

JOURNAL OF BONE AND MINERAL RESEARCH, 2010, 25 (11) :2419-2426

[10]

Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype [J].

Erlebacher, A ;

Derynck, R .

JOURNAL OF CELL BIOLOGY, 1996, 132 (1-2) :195-210

← 1 2 3 4 5 6 →