scholarly journals Amygdalin Promotes Fracture Healing through TGF-β/Smad Signaling in Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jun Ying ◽  
Qinwen Ge ◽  
Songfeng Hu ◽  
Cheng Luo ◽  
Fengyi Lu ◽  
...  

Chondrogenesis and subsequent osteogenesis of mesenchymal stem cells (MSCs) and angiogenesis at injured sites are crucial for bone fracture healing. Amygdalin, a cyanogenic glycoside compound derived from bitter apricot kernel, has been reported to inhibit IL-1β-induced chondrocyte degeneration and to stimulate blood circulation, suggesting a promising role of amygdalin in fracture healing. In this study, tibial fractures in C57BL/6 mice were treated with amygdalin. Fracture calluses were then harvested and subjected to radiographic, histological, and biomechanical testing, as well as angiography and gene expression analyses to evaluate fracture healing. The results showed that amygdalin treatment promoted bone fracture healing. Further experiments using MSC-specific transforming growth factor- (TGF-) β receptor 2 conditional knockout (KO) mice (Tgfbr2Gli1-Cre) and C3H10 T1/2 murine mesenchymal progenitor cells showed that this effect was mediated through TGF-β/Smad signaling. We conclude that amygdalin could be used as an alternative treatment for bone fractures.

2014 ◽  
Vol 29 (4) ◽  
pp. 1143-1152 ◽  
Author(s):  
Liangliang Xu ◽  
Shuo Huang ◽  
Yonghui Hou ◽  
Yang Liu ◽  
Ming Ni ◽  
...  

2018 ◽  
Vol 107 (2) ◽  
pp. 301-311 ◽  
Author(s):  
Mohammad Mousaei Ghasroldasht ◽  
Maryam M. Matin ◽  
Hossein Kazemi Mehrjerdi ◽  
Hojjat Naderi-Meshkin ◽  
Ali Moradi ◽  
...  

2018 ◽  
Vol 103 (2) ◽  
pp. 227-236 ◽  
Author(s):  
Liu Shi ◽  
Lu Feng ◽  
Yang Liu ◽  
Ji-qiang Duan ◽  
Wei-ping Lin ◽  
...  

2019 ◽  
Vol 20 (5) ◽  
pp. 1079 ◽  
Author(s):  
Sopak Supakul ◽  
Kenta Yao ◽  
Hiroki Ochi ◽  
Tomohito Shimada ◽  
Kyoko Hashimoto ◽  
...  

Pericytes are mesenchymal cells that surround the endothelial cells of small vessels in various organs. These cells express several markers, such as NG2, CD146, and PDGFRβ, and play an important role in the stabilization and maturation of blood vessels. It was also recently revealed that like mesenchymal stem cells (MSCs), pericytes possess multilineage differentiation capacity, especially myogenic, adipogenic, and fibrogenic differentiation capacities. Although some previous studies have reported that pericytes also have osteogenic potential, the osteogenesis of pericytes can still be further elucidated. In the present study, we established novel methods for isolating and culturing primary murine pericytes. An immortalized pericyte line was also established. Multilineage induction of the pericyte line induced osteogenesis, adipogenesis, and chondrogenesis of the cells in vitro. In addition, pericytes that were injected into the fracture site of a bone fracture mouse model contributed to callus formation. Furthermore, in vivo pericyte-lineage-tracing studies demonstrated that endogenous pericytes also differentiate into osteoblasts and osteocytes and contribute to bone fracture healing as a cellular source of osteogenic cells. Pericytes can be a promising therapeutic candidate for treating bone fractures with a delayed union or nonunion as well as bone diseases causing bone defects.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kai Hang ◽  
Li Ying ◽  
Jinwu Bai ◽  
Yibo Wang ◽  
Zhihui Kuang ◽  
...  

Abstract Background Globally, bone fractures are the most common musculoskeletal trauma, and approximately 8–10% of cases that fall into the categories of delayed or non-union healing. To date, there are no efficient pharmacological agents to accelerate the healing of bone fractures. Thus, it is necessary to find new strategies that accelerate bone healing and reduce the incidence of non-union or delayed fracture healing. Previous studies have revealed that the plasminogen activation system has been demonstrated to play an important role in bone metabolism. However, the function of SERPINB2 in the osteogenesis of hBMSCs remains unclear. Therefore, in this study, we investigated the effects and mechanism of SERPINB2 on osteogenic differentiation. Methods We investigated the osteogenesis effects of hBMSCs by both exogenous SerpinB2 protein and SERPINB2 gene silencing in vitro. Cell proliferation assay was used to assess the effect of exogenous SerpinB2 or SERPINB2 silencing on proliferation of hBMSCs. qPCR and Western blotting analysis detected the expression of target genes and proteins respectively. ALP staining was used to evaluated ALP activity and Alizarin Red staining (ARS) was used to evaluate mineral deposition. In vivo, a murie tibial fracture model was established, histological evaluation and radiographic analysis was used to confirm the therapeutic effects of SERPINB2 silencing in fracture healing. Statistical significance between two groups was determined by Student’s t test, one-way ANOVA or Bonferroni’s post-hoc test according to the distribution of the tested population. Results The addition of exogenous SerpinB2 protein inhibted osteoblast differentiation of hBMSCs in vitro, while SERPINB2 gene silencing significant promote osteoblast differentiation of hBMSCs in vitro. And silenced SERPINB2 gene also increased mineral deposits. Moreover, β-catenin levels were up-regulated by SERPINB2 gene depletion. And the enhancement of osteogenic differentiation induced by SERPINB2 silencing was almost inhibited by specific Wnt/β-catenin signaling pathway inhibitor. In a murine tibial fracture model, local injection of SERPINB2 siRNA improved bone fracture healing. Conclusions Taken together, these findings indicate that SERPINB2 silencing promoted osteogenic differentiation of BMSCs via the Wnt/β-catenin signaling pathway, and silenced SERPINB2 in vivo effectively promotes fracture healing, suggesting that SERPINB2 may be a novel target for bone fracture healing.


Author(s):  
Fei-fei Pan ◽  
Jiang Shao ◽  
Chuan-jian Shi ◽  
Zhi-peng Li ◽  
Wei-ming Fu ◽  
...  

Apigenin (API), a natural plant flavone, is abundantly found in common fruits and vegetables. As a bioactive flavonoid, API exhibits several activities including anti-proliferation and anti-inflammation. A recent study showed that API could retard osteoporosis progress, indicating its role in the skeletal system. However, the detailed function and mechanism remain obscure. In the present study, API was found to promote osteogenic differentiation of mesenchymal stem cells (MSCs). And further investigation showed that API could enhance the expression of the critical transcription factor β-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/β-catenin signaling. Using a rat femoral fracture model, API was found to improve new bone formation and accelerate fracture healing in vivo. In conclusion, our data demonstrated that API could promote osteogenesis in vitro and facilitate the fracture healing in vivo via activating Wnt/β-catenin signaling, indicating that API may be a promising therapeutic candidate for bone fracture repair.


Author(s):  
BRENT R IOYAH ◽  
WIDURINI DJOHAN ◽  
ERIK IDRUS

Objective: Healing of bone fractures is mediated through antioxidants; however, increased free radical levels at the site of fracture inhibit bone healing.Mangosteen peel has antioxidant, anti-inflammatory, antitumor, antiviral, antibacterial, antifungal, antihistaminic, antimalarial, and other beneficialproperties as it contains many active substances such as xanthones, anthocyanins, phenols, and tannins. In this study, we aimed to determine theeffects of mangosteen peel extract on bone fracture healing.Methods: We used six mice with left and right femoral fractures (12 femurs). Mangosteen peel extract was applied to the left femurs of the six mice attwo dosages (20 and 40 mg/kg; three femurs each) on days 2, 4, and 6 after fracture; saline was injected into the right femurs of all six mice. On day 7,all the animals were sacrificed, and femur defect diameter was evaluated using dental digital radiography.Results: The femoral defect diameter in mice treated with 40 mg/kg dose of mangosteen peel extract was less than that in mice treated with saline,although the difference was not significant.Conclusion: Application of a 40 mg/kg dose of mangosteen peel extract promotes bone fracture healing.


Sign in / Sign up

Export Citation Format

Share Document