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SMAD 7 prevents heterotopic ossification in a rat Achilles tendon injury model via regulation of endothelial–mesenchymal transition
Author(s) -
Zhang Chi,
Zhang Yang,
Zhong Biao,
Luo Congfeng
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13667
Subject(s) - smad , mesenchymal stem cell , vimentin , downregulation and upregulation , heterotopic ossification , achilles tendon , myofibroblast , pathology , medicine , cancer research , transforming growth factor , microbiology and biotechnology , biology , tendon , immunohistochemistry , anatomy , biochemistry , gene , fibrosis
The endothelial–mesenchymal transition (End MT ) is known to play a central role in the pathological process of heterotopic ossification ( HO ). Based on the ability of SMAD 7 (mothers against decapentaplegic homolog 7) to block End MT ‐related processes such as myofibroblast transformation, we hypothesized that SMAD 7 may be a potential therapeutic target for HO . We constructed a lentivirus overexpressing SMAD 7 and tested on rat aortic endothelial cells for optimal titre and transduction efficiency. The lentivirus was then injected into a surgical rat model of Achilles tendon injury. Expression of endothelial markers and mesenchymal markers at the injury sites was subsequently quantified by qPCR and western analysis. Lentiviral delivery of SMAD 7 in vivo resulted in an upregulation of endothelial markers ( CD 31, VE ‐cadherin) and a downregulation of mesenchymal markers (N‐cadherin and vimentin), suggesting that End MT is blocked due to local SMAD 7 overexpression. The difference is more apparent at 10 weeks than at 6 weeks after surgery. X‐ray imaging and histological staining further confirmed the absence of ossified structure in the tendon tissue injected with SMAD 7‐delivering lentivirus, as opposed to the control groups. Post‐surgical HO may be prevented in vivo by local delivery of SMAD 7 without affecting the normal wound‐healing process. These data advance our understanding of the HO process at the molecular level, and provide additional avenues for the prevention and treatment of postoperative HO .