TY - JOUR
T1 - Transcriptional profiling of intramembranous and endochondral ossification after fracture in mice
AU - Coates, Brandon A.
AU - McKenzie, Jennifer A.
AU - Buettmann, Evan G.
AU - Liu, Xiaochen
AU - Gontarz, Paul M.
AU - Zhang, Bo
AU - Silva, Matthew J.
N1 - Funding Information:
This work was supported by funding from NIAMS ( R01 AR050211 , P30 AR057235 , and P30 AR074992 ) and NIBIB ( T32 EB018266 ). The authors would like to thank the cores and staff of the Washington University Musculoskeletal Research Center for their assistance. Specifically, thanks to Crystal Idleburg and Samantha Coleman for histological processing and sectioning and Dan Leib for assistance in radiograph image acquisition. Histology slides were imaged with the Nanozoomer at Alafi Neuroimaging Core (S10 RR027552). RNA sequencing was performed by the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine which is partially supported by NCI ( P30 CA91842 ) and NCRR ( UL1 TR000448 ).
Funding Information:
The authors would like to disclose that Matthew Silva has past research grant support from Merck Co. (2014–2017) and occasional royalty income from Springer.
Funding Information:
This work was supported by funding from NIAMS (R01 AR050211, P30 AR057235, and P30 AR074992) and NIBIB (T32 EB018266). The authors would like to thank the cores and staff of the Washington University Musculoskeletal Research Center for their assistance. Specifically, thanks to Crystal Idleburg and Samantha Coleman for histological processing and sectioning and Dan Leib for assistance in radiograph image acquisition. Histology slides were imaged with the Nanozoomer at Alafi Neuroimaging Core (S10 RR027552). RNA sequencing was performed by the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine which is partially supported by NCI (P30 CA91842) and NCRR (UL1 TR000448). Brandon Coates: Conceptualization, Formal Analysis, Investigation, Data Curation, Writing ?Original Draft, Writing ? Review & Editing, Visualization. Jennifer McKenzie: Conceptualization, Investigation, Writing ?Original Draft, Writing ? Review & Editing. Evan Buettmann: Investigation, Writing ? Review & Editing. Xiaochen Liu: Investigation, Writing ? Review & Editing. Paul Gontarz: Software, Formal Analysis, Data Curation. Bo Zhang: Software, Formal Analysis, Data Curation, Writing ? Review & Editing. Matthew Silva: Conceptualization, Resources, Writing ?Original Draft, Writing ? Review & Editing, Supervision, Funding Acquisition. The authors would like to disclose that Matthew Silva has past research grant support from Merck Co. (2014?2017) and occasional royalty income from Springer. All other authors have no financial conflicts of interest with the submission of this manuscript.? Grant supporters: NIAMS (R01 AR050211, P30 AR057235, P30 AR074992), NIBIB (T32 EB018266). Funding supporters played no role in study design, collection, analysis and interpretation of data, or writing of this report.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10
Y1 - 2019/10
N2 - Bone fracture repair represents an important clinical challenge with nearly 1 million non-union fractures occurring annually in the U.S. Gene expression differs between non-union and healthy repair, suggesting there is a pattern of gene expression that is indicative of optimal repair. Despite this, the gene expression profile of fracture repair remains incompletely understood. In this work, we used RNA-seq of two well-established murine fracture models to describe gene expression of intramembranous and endochondral bone formation. We used top differentially expressed genes, enriched gene ontology terms and pathways, callus cellular phenotyping, and histology to describe and contrast these bone formation processes across time. Intramembranous repair, as modeled by ulnar stress fracture, and endochondral repair, as modeled by femur full fracture, exhibited vastly different transcriptional profiles throughout repair. Stress fracture healing had enriched differentially expressed genes associated with bone repair and osteoblasts, highlighting the strong osteogenic repair process of this model. Interestingly, the PI3K-Akt signaling pathway was one of only a few pathways uniquely enriched in stress fracture repair. Full fracture repair involved a higher level of inflammatory and immune cell related genes than did stress fracture repair. Full fracture repair also differed from stress fracture in a robust downregulation of ion channel genes following injury, the role of which in fracture repair is unclear. This study offers a broad description of gene expression in intramembranous and endochondral ossification across several time points throughout repair and suggests several potentially intriguing genes, pathways, and cells whose role in fracture repair requires further study.
AB - Bone fracture repair represents an important clinical challenge with nearly 1 million non-union fractures occurring annually in the U.S. Gene expression differs between non-union and healthy repair, suggesting there is a pattern of gene expression that is indicative of optimal repair. Despite this, the gene expression profile of fracture repair remains incompletely understood. In this work, we used RNA-seq of two well-established murine fracture models to describe gene expression of intramembranous and endochondral bone formation. We used top differentially expressed genes, enriched gene ontology terms and pathways, callus cellular phenotyping, and histology to describe and contrast these bone formation processes across time. Intramembranous repair, as modeled by ulnar stress fracture, and endochondral repair, as modeled by femur full fracture, exhibited vastly different transcriptional profiles throughout repair. Stress fracture healing had enriched differentially expressed genes associated with bone repair and osteoblasts, highlighting the strong osteogenic repair process of this model. Interestingly, the PI3K-Akt signaling pathway was one of only a few pathways uniquely enriched in stress fracture repair. Full fracture repair involved a higher level of inflammatory and immune cell related genes than did stress fracture repair. Full fracture repair also differed from stress fracture in a robust downregulation of ion channel genes following injury, the role of which in fracture repair is unclear. This study offers a broad description of gene expression in intramembranous and endochondral ossification across several time points throughout repair and suggests several potentially intriguing genes, pathways, and cells whose role in fracture repair requires further study.
KW - Animal models
KW - Bone
KW - Fracture repair
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85071711588&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2019.07.022
DO - 10.1016/j.bone.2019.07.022
M3 - Article
C2 - 31369916
AN - SCOPUS:85071711588
VL - 127
SP - 577
EP - 591
JO - Bone
JF - Bone
SN - 8756-3282
ER -