Low-molecular-weight estrogenic phytoprotein suppresses osteoporosis development through positive modulation of skeletal estrogen receptors  

作　　者：John Akrofi Kubi Augustine Suurinobah Brah Kenneth Man Chee Cheung Andy Chun Hang Chen Yin Lau Lee Kai-Fai Lee Wei Qiao Yibin Feng 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),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,PR China [4]Shenzhen Key Laboratory of Fertility Regulation,Reproductive Medicine Center,HKU-Shenzhen Hospital,Shenzhen,PR China [5]Applied Oral Sciences and Community Dental Care,Faculty of Dentistry,PR China [6]School of Chinese Medicine,Li Ka Shing Faculty of Medicine,The University of Hong Kong(HKU),PR China

出　　处：《Bioactive Materials》2024年第12期299-315,共17页生物活性材料（英文）

基　　金：supported by the Seed Fund for Translational and Applied Research from the University Research Committee(URC),The University of Hong Kong(HKU),Hong Kong China(Project Codes:201910160024 and 202010160009).

摘　　要：Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women.Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators(SERMs)has been associated with various clinical drawbacks.We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein,called HKUOT-S2 protein(32 kDa),from Dioscorea opposita Thunb that can accelerate bone defect healing.Here,we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors(ERs)ERα,ERβ,and GPR30 expressions in vivo.Also,HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers,ALP,and RUNX2 expressions,ALP activity,and osteoblast biomineralization in vitro.Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions,osteoblasts differentiation,and functions.Finally,we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties.Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis.Currently,there is no or limited data if any,on osteoanabolic SERMs.The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.

关 键 词：Ovariectomy(ovx) OSTEOPOROSIS Osteoblast functions Estrogen receptors(ERs) HKUOT-S2 protein 

分 类 号：R681[医药卫生—骨科学]