A new osteogenic protein isolated from Dioscorea opposita Thunb accelerates bone defect healing through the mTOR signaling axis  

作　　者：John Akrofi Kubi Augustine Suurinobah Brah Kenneth Man Chee Cheung Yin Lau Lee Kai-Fai Lee Stephen Cho Wing Sze Wei Qiao Kelvin Wai-Kwok Yeung 

机构地区：[1]Department of Orthopaedics and Traumatology,Li Ka Shing Faculty of Medicine,The University of Hong Kong(HKU),Hong Kong S.A.R.,PR China [2]Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma,HKU-Shenzhen Hospital,Shenzhen,518053,PR China [3]Department of Obstetrics and Gynaecology,Li Ka Shing Faculty of Medicine,HKU,21 Sassoon Road,Hong Kong S.A.R,PR China [4]Shenzhen Key Laboratory of Fertility Regulation,Reproductive Medicine Center,HKU-Shenzhen Hospital,Shenzhen,PR China [5]Department of Biology,Faculty of Science,Hong Kong Baptist University,Kowloon Tong,Hong Kong S.A.R,PR China [6]Golden Meditech Center for NeuroRegeneration Sciences,Hong Kong Baptist University,Kowloon Tong,Hong Kong S.A.R,PR China [7]Applied Oral Sciences and Community Dental Care,Faculty of Dentistry,Hong Kong S.A.R,PR China

出　　处：《Bioactive Materials》2023年第9期429-446,共18页生物活性材料（英文）

基　　金：All animal experimental procedures were carried out strictly according to the protocol approved by the University of Hong Kong(HKU)Ethics Committee,Committee on the Use of Live Animals in Teaching and Research(CULATR),(CULATR 5502-20).

摘　　要：Delayed bone defect repairs lead to severe health and socioeconomic impacts on patients. Hence, there are increasing demands for medical interventions to promote bone defect healing. Recombinant proteins such as BMP-2 have been recognized as one of the powerful osteogenic substances that promote mesenchymal stem cells (MSCs) to osteoblast differentiation and are widely applied clinically for bone defect repairs. However, recent reports show that BMP-2 treatment has been associated with clinical adverse side effects such as ectopic bone formation, osteolysis and stimulation of inflammation. Here, we have identified one new osteogenic protein, named ‘HKUOT-S2’ protein, from Dioscorea opposita Thunb. Using the bone defect model, we have shown that the HKUOT-S2 protein can accelerate bone defect repair by activating the mTOR signaling axis of MSCs-derived osteoblasts and increasing osteoblastic biomineralization. The HKUOT-S2 protein can also modulate the transcriptomic changes of macrophages, stem cells, and osteoblasts, thereby enhancing the crosstalk between the polarized macrophages and MSCs-osteoblast differentiation to facilitate osteogenesis. Furthermore, this protein had no toxic effects in vivo. We have also identified HKUOT-S2 peptide sequence TKSSLPGQTK as a functional osteogenic unit that can promote osteoblast differentiation in vitro. The HKUOT-S2 protein with robust osteogenic activity could be a potential alternative osteoanabolic agent for promoting osteogenesis and bone defect repairs. We believe that the HKUOT-S2 protein may potentially be applied clinically as a new class of osteogenic agent for bone defect healing.

关 键 词：Dioscorea spp protein Mesenchymal stem cells(MSCs) Osteoblast differentiation Bone mineral density(BMD) Bone defect repair mTOR signaling pathway 

分 类 号：R318[医药卫生—生物医学工程]