Jianmin Liu1, Longyang Ma1, Wengang Dong1, Gongliang Du1, Xingbo Dang2. 1. Department of Emergency Surgery, Shanxi Provincial People's Hospital, Xi'an, Shanxi, 710068, China. 2. Department of Emergency Surgery, Shanxi Provincial People's Hospital, Xi'an, Shanxi, 710068, China. dangxb2006@163.com.
Abstract
BACKGROUND: Bone defect difficult to manage clinically and it is a big challenge to repair it. Secondary metabolites source from herb has shown potential for the treatment of bone defect. METHODS: Mesenchymal stem cells (MSCs) were isolated from mice and incubated with urolithin A (UA) (10, 25, and 50 µg/mL). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to estimate apoptosis and mineralisation was evaluated by alkaline phosphatase assay and alizarin red S staining. A middle femoral defect was induced in mice and bone tissue was prepared for endochondral ossification by treating with UA. The effect of UA was estimated by determining markers of osteoblast proliferation in serum and micro-computed tomography to analyse bone defects. RESULTS: UA enhanced mineralisation of MSCs and osteogenic gene markers in MSCs in vitro. Also, the bone defect score and bone mineral density were improved by UA. Moreover, UA ameliorated the altered Wnt3a protein and histopathological changes in bone defect mice. CONCLUSION: Presented report conclude that UA enhances osteoblast proliferation in bone-defect mice by activating the Wnt pathway.
BACKGROUND: Bone defect difficult to manage clinically and it is a big challenge to repair it. Secondary metabolites source from herb has shown potential for the treatment of bone defect. METHODS: Mesenchymal stem cells (MSCs) were isolated from mice and incubated with urolithin A (UA) (10, 25, and 50 µg/mL). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to estimate apoptosis and mineralisation was evaluated by alkaline phosphatase assay and alizarin red S staining. A middle femoral defect was induced in mice and bone tissue was prepared for endochondral ossification by treating with UA. The effect of UA was estimated by determining markers of osteoblast proliferation in serum and micro-computed tomography to analyse bone defects. RESULTS: UA enhanced mineralisation of MSCs and osteogenic gene markers in MSCs in vitro. Also, the bone defect score and bone mineral density were improved by UA. Moreover, UA ameliorated the altered Wnt3a protein and histopathological changes in bone defect mice. CONCLUSION: Presented report conclude that UA enhances osteoblast proliferation in bone-defect mice by activating the Wnt pathway.
Authors: Phuong N Dang; Samuel Herberg; Davood Varghai; Hooman Riazi; Daniel Varghai; Alexandra McMillan; Amad Awadallah; Lauren M Phillips; Oju Jeon; Minh K Nguyen; Neha Dwivedi; Xiaohua Yu; William L Murphy; Eben Alsberg Journal: Stem Cells Transl Med Date: 2017-06-08 Impact factor: 6.940