TY - JOUR
T1 - Lineage-Specific Wnt Reporter Elucidates Mesenchymal Wnt Signaling during Bone Repair
AU - Chang, Leslie
AU - Zhang, Lei
AU - Xu, Jiajia
AU - Meyers, Carolyn A.
AU - Li, Zhu
AU - Yan, Noah
AU - Zou, Erin
AU - James, Aaron W.
N1 - Funding Information:
Supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases grants R01 AR070773 (A.W.J.) and K08 AR068316 (A.W.J.), US Army Medical Research Acquisition Activity through the Peer Reviewed Medical Research Program W81XWH-180109121 (A.W.J.), American Cancer Society Research Scholar grant RSG-18-027-01-CSM (A.W.J.), the Orthopedic Research and Education Foundation (with funding provided by the Musculoskeletal Transplant Foundation; A.W.J.), the Maryland Stem Cell Research Foundation (A.W.J.), and the Musculoskeletal Transplant Foundation (A.W.J.).
Publisher Copyright:
© 2018 American Society for Investigative Pathology
PY - 2018/10
Y1 - 2018/10
N2 - β-Catenin–dependent Wnt signaling controls numerous aspects of skeletal development and postnatal bone repair. Currently available transgenic Wnt reporter mice allow for visualization of global canonical Wnt signaling activity within skeletal tissues, without delineation of cell type. This is particularly important in a bone repair context, in which the inflammatory phase can obscure the visualization of mesenchymal cell types of interest. To tackle the issue of tissue-specific Wnt signaling, we have generated and characterized a transgenic mouse strain [termed paired related homeobox 1 (Prx1)–Wnt–green fluorescent protein (GFP), by crossing a previously validated Prx1-Cre strain with a nuclear fluorescent reporter driven by T-cell factor/lymphoid enhancer factor activity (Rosa26-Tcf/Lef-LSL-H2B-GFP)]. Prx1-Wnt-GFP animals were subject to three models of long bone and membranous bone repair (displaced forelimb fracture, tibial cortical defect, and frontal bone defect). Results showed that, irrespective of bone type, locoregional mesenchymal cell activation of Wnt signaling occurs in a defined temporospatial pattern among Prx1-Wnt-GFP mice. In summary, Prx1-Wnt-GFP reporter animals allow for improved visualization, spatial discrimination, and facile quantification of Wnt-activated mesenchymal cells within models of adult bone repair.
AB - β-Catenin–dependent Wnt signaling controls numerous aspects of skeletal development and postnatal bone repair. Currently available transgenic Wnt reporter mice allow for visualization of global canonical Wnt signaling activity within skeletal tissues, without delineation of cell type. This is particularly important in a bone repair context, in which the inflammatory phase can obscure the visualization of mesenchymal cell types of interest. To tackle the issue of tissue-specific Wnt signaling, we have generated and characterized a transgenic mouse strain [termed paired related homeobox 1 (Prx1)–Wnt–green fluorescent protein (GFP), by crossing a previously validated Prx1-Cre strain with a nuclear fluorescent reporter driven by T-cell factor/lymphoid enhancer factor activity (Rosa26-Tcf/Lef-LSL-H2B-GFP)]. Prx1-Wnt-GFP animals were subject to three models of long bone and membranous bone repair (displaced forelimb fracture, tibial cortical defect, and frontal bone defect). Results showed that, irrespective of bone type, locoregional mesenchymal cell activation of Wnt signaling occurs in a defined temporospatial pattern among Prx1-Wnt-GFP mice. In summary, Prx1-Wnt-GFP reporter animals allow for improved visualization, spatial discrimination, and facile quantification of Wnt-activated mesenchymal cells within models of adult bone repair.
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U2 - 10.1016/j.ajpath.2018.07.003
DO - 10.1016/j.ajpath.2018.07.003
M3 - Article
C2 - 30031726
AN - SCOPUS:85053763552
SN - 0002-9440
VL - 188
SP - 2155
EP - 2163
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 10
ER -