TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

被引:1185
作者
Wu, Mengrui [1 ]
Chen, Guiqian [1 ,2 ]
Li, Yi-Ping [1 ]
机构
[1] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
[2] Cornell Univ, Weil Cornell Med, Bruke Med Res Inst, Dept Neurol, White Plains, NY USA
来源
BONE RESEARCH | 2016年 / 4卷
关键词
GROWTH-FACTOR-BETA; MESENCHYMAL STEM-CELLS; MORPHOGENETIC PROTEIN-2 EXPRESSION; IA RECEPTOR BMPRIA; ENDOCHONDRAL BONE; OSTEOGENIC DIFFERENTIATION; INDIAN-HEDGEHOG; CHONDROCYTE DIFFERENTIATION; AXIAL SKELETON; II RECEPTOR;
D O I
10.1038/boneres.2016.9
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Transforming growth factor-beta (TGF-beta) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-beta s and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-beta/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-beta and BMP signaling is controlled by multiple factors, including the ubiquitin-proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-beta and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-beta and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-beta/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-beta/BMP signaling and several critical cytokines' signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-beta/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-beta/BMP signaling.
引用
收藏
页数:21
相关论文
共 258 条
[11]   PTH battles TGF-β in bone [J].
Atfi, Azeddine ;
Baron, Roland .
NATURE CELL BIOLOGY, 2010, 12 (03) :205-207
[12]   Conditional deletion of the TGF-β type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones [J].
Baffi, MO ;
Slattery, E ;
Sohn, P ;
Moses, HL ;
Chytil, A ;
Serra, R .
DEVELOPMENTAL BIOLOGY, 2004, 276 (01) :124-142
[13]   Bone Morphogenetic Protein-2 Decreases MicroRNA-30b and MicroRNA-30c to Promote Vascular Smooth Muscle Cell Calcification [J].
Balderman, Joshua A. F. ;
Lee, Hae-Young ;
Mahoney, Christopher E. ;
Handy, Diane E. ;
White, Kevin ;
Annis, Sofia ;
Lebeche, Djamel ;
Hajjar, Roger J. ;
Loscalzo, Joseph ;
Leopold, Jane A. .
JOURNAL OF THE AMERICAN HEART ASSOCIATION, 2012, 1 (06) :e003905
[14]   Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis [J].
Bandyopadhyay, Amitabha ;
Tsuji, Kunikazu ;
Cox, Karen ;
Harfe, Brian D. ;
Rosen, Vicki ;
Tabin, Clifford J. .
PLOS GENETICS, 2006, 2 (12) :2116-2130
[15]   Bone development [J].
Berendsen, Agnes D. ;
Olsen, Bjorn R. .
BONE, 2015, 80 :14-18
[16]   The emerging role of TGF-β superfamily coreceptors in cancer [J].
Bernabeu, Carmelo ;
Lopez-Novoa, Jose M. ;
Quintanilla, Miguel .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2009, 1792 (10) :954-973
[17]   Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP) [J].
Billings, Paul C. ;
Fiori, Jennifer L. ;
Bentwood, Jennifer L. ;
O'Connell, Michael P. ;
Jiao, Xiangyang ;
Nussbaum, Burton ;
Caron, Robert J. ;
Shore, Eileen M. ;
Kaplan, Frederick S. .
JOURNAL OF BONE AND MINERAL RESEARCH, 2008, 23 (03) :305-313
[18]   Mutational analysis of the ACVR1 gene in Italian patients affected with fibrodysplasia ossificans progressiva: confirmations and advancements [J].
Bocciardi, Renata ;
Bordo, Domenico ;
Di Duca, Marco ;
Di Rocco, Maja ;
Ravazzolo, Roberto .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (03) :311-318
[19]   Altered Expression of Circulating MicroRNA in Plasma of Patients with Primary Osteoarthritis and In Silico Analysis of Their Pathways [J].
Borgonio Cuadra, Veronica M. ;
Celia Gonzalez-Huerta, Norma ;
Romero-Cordoba, Sandra ;
Hidalgo-Miranda, Alfredo ;
Miranda-Duarte, Antonio .
PLOS ONE, 2014, 9 (06)
[20]   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