TY - JOUR
T1 - Growth plate expression profiling
T2 - Large and small breed dogs provide new insights in endochondral bone formation
AU - Teunissen, Michelle
AU - Riemers, Frank M.
AU - van Leenen, Dik
AU - Groot Koerkamp, Marian J.A.
AU - Meij, Björn P.
AU - Alblas, Jacqueline
AU - Penning, Louis C.
AU - Miranda-Bedate, Alberto
AU - Tryfonidou, Marianna A.
N1 - Funding Information:
The authors wish to acknowledge Harry van Engelen for his valuable technical assistance in sampling the material. Funding was provided by the AO Foundation (Grant S-10-48T) and supported by the Dutch Arthritis Foundation (LLP 22 and 12). The founding body provided advice on the study design prior to initiation of the project.
Publisher Copyright:
© 2017 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals Inc. on behalf of the Orthopaedic Research Society.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The difference in the adult height of mammals, and hence in endochondral bone formation, is not yet fully understood and may serve to identify targets for bone and cartilage regeneration. In line with this hypothesis, the intra-species disparity between the adult height of Great Danes and Miniature Poodles was investigated at a transcriptional level. Microarray analysis of the growth plate of five Great Danes and five Miniature Poodles revealed 2,981 unique genes that were differentially expressed, including many genes with an unknown role in skeletal development. A signaling pathway impact analysis indicated activation of the cell cycle, extracellular matrix receptor interaction and the tight junction pathway, and inhibition of pathways associated with inflammation and the complement cascade. In additional validation steps, the gene expression profile of the separate growth plate zones for both dog breeds were determined. Given that the BMP signaling is known for its crucial role in skeletal development and fracture healing, and BMP-2 is used in orthopaedic and spine procedures for bone augmentation, further investigations concentrated on the BMP pathway.The canonical BMP-2 and BMP-6 signaling pathway was activated in the Great Danes compared to Miniature Poodles. In conclusion, investigating the differential expression of genes involved in endochondral bone formation in small and large breed dogs, could be a game changing strategy to provide new insights in growth plate development and identify new targets for bone and cartilage regeneration.
AB - The difference in the adult height of mammals, and hence in endochondral bone formation, is not yet fully understood and may serve to identify targets for bone and cartilage regeneration. In line with this hypothesis, the intra-species disparity between the adult height of Great Danes and Miniature Poodles was investigated at a transcriptional level. Microarray analysis of the growth plate of five Great Danes and five Miniature Poodles revealed 2,981 unique genes that were differentially expressed, including many genes with an unknown role in skeletal development. A signaling pathway impact analysis indicated activation of the cell cycle, extracellular matrix receptor interaction and the tight junction pathway, and inhibition of pathways associated with inflammation and the complement cascade. In additional validation steps, the gene expression profile of the separate growth plate zones for both dog breeds were determined. Given that the BMP signaling is known for its crucial role in skeletal development and fracture healing, and BMP-2 is used in orthopaedic and spine procedures for bone augmentation, further investigations concentrated on the BMP pathway.The canonical BMP-2 and BMP-6 signaling pathway was activated in the Great Danes compared to Miniature Poodles. In conclusion, investigating the differential expression of genes involved in endochondral bone formation in small and large breed dogs, could be a game changing strategy to provide new insights in growth plate development and identify new targets for bone and cartilage regeneration.
KW - BMP pathway
KW - canine
KW - endochondral bone formation
KW - growth plate
KW - microarray
UR - http://www.scopus.com/inward/record.url?scp=85042908645&partnerID=8YFLogxK
U2 - 10.1002/jor.23647
DO - 10.1002/jor.23647
M3 - Article
AN - SCOPUS:85042908645
SN - 0736-0266
VL - 36
SP - 138
EP - 148
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 1
ER -