Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells
机构：[1]Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.[2]Department of Orthopaedics, Chengdu Second People's Hospital, Chengdu 610017, China.[3]Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.[4]College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.[5]Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.[6]Department of Orthopaedics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.[7]Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Heterotopic ossification (HO) is defined as the generation of pathological ectopic bony structures in soft tissues, but the molecular mechanisms of tendon HO are not fully revealed. Hedgehog (Hh) signalling is reportedly critical in hereditary HO. Our study focuses on the role of Hh signalling in the formation of trauma-induced tendon ossification. In this study, samples of healthy tendons and injured tendons from C57BL/6J female mice at 1, 4, 7, and 10 weeks after Achilles tenotomy were collected for quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical analysis (IHC). At 1, 4, 7, and 10 weeks postinjury, tendon samples from the mice administered with vehicle, GANT58 (a GLI antagonist), or SAG (a smoothened agonist) were harvested for micro-CT, histological staining, qRT-PCR, and IHC. Rat tendon-derived stem cells (TDSCs) treated with vehicle, GANT58, or SAG were used to induce osteogenic and chondrogenic differentiation in vitro for qRT-PCR, alkaline phosphatase staining, Alcian blue staining, and reactive oxygen species (ROS) levels measurement. We found that Hh signalling is remarkably activated during the formation of trauma-induced tendon ossification in the model of Achilles tenotomy. The in vitro and in vivo assays both confirm that downregulation of Hh signalling significantly suppresses osteogenesis and chondrogenesis to inhibit tendon ossification, while upregulation of Hh signalling promotes this process. Under osteogenic induction, Hh signalling regulates antioxidant pathway and affects ROS generation of TDSCs. Collectively, Hh signalling contributes to trauma-induced tendon ossification and affects ROS generation through antioxidant pathway in osteogenic differentiation of TDSCs, indicating that targeting Hh signalling by GANT58 may be a potential treatment for trauma-induced tendon ossification.
基金：
This research received funding support from National Natural Science Foundation of China
(No. 82072430) to K.Z., Outstanding Youths Development Scheme of Nanfang Hospital, Southern
Medical University (No. 2019J005) to K.Z., Innovation Team and Talents Cultivation Program of
National Administration of Traditional Chinese Medicine (No. ZYYCXTD-C-202003) to C.C. and
Sanming Project of Medicine in Shenzhen (No. SZZYSM202108013) to C.C.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|2 区医学
小类|2 区生化与分子生物学2 区药物化学2 区食品科技
最新[2025]版：
大类|2 区医学
小类|2 区生化与分子生物学2 区药物化学2 区食品科技
第一作者：
第一作者机构：[1]Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
共同第一作者：
通讯作者：
通讯机构：[1]Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.[7]Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
推荐引用方式(GB/T 7714)：
Li Guanzhi,Deng Ye,Li Kaiqun,et al.Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells[J].Antioxidants (Basel, Switzerland).2022,11(11):doi:10.3390/antiox11112265.
APA：
Li Guanzhi,Deng Ye,Li Kaiqun,Liu Yuchen,Wang Ling...&Yu Bin.(2022).Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells.Antioxidants (Basel, Switzerland),11,(11)
MLA：
Li Guanzhi,et al."Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells".Antioxidants (Basel, Switzerland) 11..11(2022)
