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Type: Journal article
Title: Enhanced BMP signalling causes growth plate cartilage dysrepair in rats
Author: Su, Y.-W.
Wong, D.S.K.
Fan, J.
Chung, R.
Wang, L.
Chen, Y.
Xian, C.H.
Yao, L.
Wang, L.
Foster, B.K.
Xu, J.
Xian, C.J.
Citation: Bone, 2021; 145:115874-1-115874-13
Publisher: Elsevier
Issue Date: 2021
ISSN: 8756-3282
Statement of
Yu-Wen Su, Derick S.K. Wong, Jian Fan, Rosa Chung, Liping Wang, Yuhui Chen ... et al.
Abstract: Growth plate cartilage injuries often result in bony repair at the injury site and premature mineralization at the uninjured region causing bone growth defects, for which underlying mechanisms are unclear. With the prior microarray study showing upregulated bone morphogenetic protein (BMP) signalling during the injury site bony repair and with the known roles of BMP signalling in bone healing and growth plate endochondral ossification, this study used a rat tibial growth plate drill-hole injury model with or without systemic infusion of BMP antagonist noggin to investigate roles of BMP signalling in injury repair responses within the injury site and in the adjacent "uninjured" cartilage. At days 8, 14 and 35 post-injury, increased expression of BMP members and receptors and enhanced BMP signalling (increased levels of phosphorylated (p)-Smad1/5/8) were found during injury site bony repair. After noggin treatment, injury site bony repair at days 8 and 14 was reduced as shown by micro-CT and histological analyses and lower mRNA expression of osteogenesis-related genes Runx2 and osteocalcin (by RT-PCR). At the adjacent uninjured cartilage, the injury caused increases in the hypertrophic zone/proliferative zone height ratio and in mRNA expression of hypertrophy marker collagen-10, but a decrease in chondrogenesis marker Sox9 at days 14 and/or 35, which were accompanied by increased BMP signalling (increased levels of pSmad1/5/8 protein and BMP7, BMPR1a and target gene Dlx5 mRNA). Noggin treatment reduced the hypertrophic zone/proliferative zone height ratio and collagen-10 mRNA expression, but increased collagen-2 mRNA levels at the adjacent growth plate. This study has identified critical roles of BMP signalling in the injury site bony repair and in the hypertrophic degeneration of the adjacent growth plate in a growth plate drill-hole repair model. Moreover, suppressing BMP signalling can potentially attenuate the undesirable bony repair at injury site and suppress the premature hypertrophy but potentially rescue chondrogenesis at the adjacent growth plate.
Keywords: BMP signalling
Growth plate
Injury repair
bone growth defects
cartilage degeneration
Rights: © 2021 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bone.2021.115874
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